rs11571315

Positions:

• chr2-203866178-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696479.1(CTLA4):​c.48-1740T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,016 control chromosomes in the GnomAD database, including 23,130 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 (23130 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000696479.1	c.48-1740T>C		intron_variant				ENSP00000512655

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83040 AN: 151898 Hom.: 23132 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.546 AC: 83065 AN: 152016 Hom.: 23130 Cov.: 32 AF XY: 0.541 AC XY: 40194 AN XY: 74284

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.598

Alfa AF: 0.591 Hom.: 48768

Bravo AF: 0.548

Asia WGS AF: 0.532 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11571315; hg19: chr2-204730901;