rs11571317

chr2-203867285-C-T

Variant summary

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

The ENST00000696479.1(CTLA4):c.48-633C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 152,246 control chromosomes in the GnomAD database, including 291 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 0.051 (291 hom., cov: 33)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTLA4	ENST00000696479.1	c.48-633C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7827 AN: 152128 Hom.: 291 Cov.: 33

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0731

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

GnomAD4 genome AF: 0.0514 AC: 7822 AN: 152246 Hom.: 291 Cov.: 33 AF XY: 0.0477 AC XY: 3553 AN XY: 74442

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.0719

Alfa AF: 0.0787 Hom.: 504

Bravo AF: 0.0529

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.8
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11571317; hg19: chr2-204732008;