rs11571291

Variant names:

• chr2-203856409-T-C
• rs11571291
• ENST00000696479.1:c.47+2333T>C

Variant summary

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

The ENST00000696479.1(CTLA4):​c.47+2333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,918 control chromosomes in the GnomAD database, including 11,670 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 0.39 (11670 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 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+2333T>C		intron_variant	Intron 1 of 4			ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58723 AN: 151800 Hom.: 11671 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.387 AC: 58743 AN: 151918 Hom.: 11670 Cov.: 32 AF XY: 0.384 AC XY: 28511 AN XY: 74246

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.437

Alfa AF: 0.416 Hom.: 11633

Bravo AF: 0.387

Asia WGS AF: 0.451 AC: 1566 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11571291; hg19: chr2-204721132;