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NM_005214.5(CTLA4):c.567+1G>A AND Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 16, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000558959.2

Allele description [Variation Report for NM_005214.5(CTLA4):c.567+1G>A]

NM_005214.5(CTLA4):c.567+1G>A

Genes:
LOC129935461:ATAC-STARR-seq lymphoblastoid active region 17016 [Gene]
CTLA4:cytotoxic T-lymphocyte associated protein 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q33.2
Genomic location:
Preferred name:
NM_005214.5(CTLA4):c.567+1G>A
HGVS:
  • NC_000002.12:g.203871488G>A
  • NG_011502.1:g.8703G>A
  • NG_168474.1:g.135G>A
  • NM_001037631.3:c.457+555G>A
  • NM_005214.5:c.567+1G>AMANE SELECT
  • LRG_1220t1:c.567+1G>A
  • LRG_1220:g.8703G>A
  • NC_000002.11:g.204736211G>A
  • NM_005214.4:c.567+1G>A
Links:
dbSNP: rs1553657487
NCBI 1000 Genomes Browser:
rs1553657487
Molecular consequence:
  • NM_001037631.3:c.457+555G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_005214.5:c.567+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
Synonyms:
CTLA4 HAPLOINSUFFICIENCY WITH AUTOIMMUNE INFILTRATION; Autoimmune lymphoproliferative syndrome type V; Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0014493; MedGen: C4015214; Orphanet: 436159; OMIM: 616100

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000655459Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 16, 2017) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000655459.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change affects a donor splice site in the last intron (intron 3) of the CTLA4 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a CTLA4-related disease. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on CTLA4 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024