2-203858029-G-T

Variant names:

• chr2-203858029-G-T
• rs926169
• ENST00000696479.1:c.47+3953G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696479.1(CTLA4):​c.47+3953G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,008 control chromosomes in the GnomAD database, including 12,886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12886 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 19 publications found

Genes affected

CTLA4 (HGNC:2505): (cytotoxic T-lymphocyte associated protein 4) This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008]

CTLA4 Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTLA4	ENST00000696479.1		c.47+3953G>T		intron	N/A	ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61493 AN: 151890 Hom.: 12874 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.366

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.405 AC: 61549 AN: 152008 Hom.: 12886 Cov.: 32 AF XY: 0.411 AC XY: 30529 AN XY: 74290

African (AFR) AF: 0.366 AC: 15191 AN: 41460

American (AMR) AF: 0.420 AC: 6413 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3312 AN: 5168

South Asian (SAS) AF: 0.336 AC: 1619 AN: 4816

European-Finnish (FIN) AF: 0.522 AC: 5506 AN: 10550

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27182 AN: 67956

Other (OTH) AF: 0.365 AC: 770 AN: 2108

Alfa AF: 0.374 Hom.: 5589

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs926169; hg19: chr2-204722752;