ENST00000696479.1:c.47+2953T>C

Variant names:

• chr2-203857029-T-C
• rs1024161
• ENST00000696479.1:c.47+2953T>C

Variant summary

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

The ENST00000696479.1(CTLA4):​c.47+2953T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,970 control chromosomes in the GnomAD database, including 23,314 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 0.55 (23314 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 40 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=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000696479.1	c.47+2953T>C		intron_variant	Intron 1 of 4			ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83394 AN: 151852 Hom.: 23309 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.549 AC: 83432 AN: 151970 Hom.: 23314 Cov.: 32 AF XY: 0.544 AC XY: 40382 AN XY: 74270

African (AFR) AF: 0.505 AC: 20922 AN: 41450

American (AMR) AF: 0.560 AC: 8557 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2326 AN: 3464

East Asian (EAS) AF: 0.355 AC: 1838 AN: 5172

South Asian (SAS) AF: 0.660 AC: 3185 AN: 4828

European-Finnish (FIN) AF: 0.461 AC: 4872 AN: 10568

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39740 AN: 67898

Other (OTH) AF: 0.603 AC: 1273 AN: 2110

Alfa AF: 0.576 Hom.: 81713

Bravo AF: 0.550

Asia WGS AF: 0.541 AC: 1884 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.65
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs1024161; hg19: chr2-204721752;