2-203857029-T-C

Position:

• chr2-203857029-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.203857029T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000696479.1	c.47+2953T>C		intron_variant				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

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.603

Alfa AF: 0.582 Hom.: 38564

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1024161; hg19: chr2-204721752;