rs2162610

Positions:

• chr2-203854006-C-A
• chr2-203854006-C-G

Variant summary

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

The ENST00000696479.1(CTLA4):​c.-24C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,092 control chromosomes in the GnomAD database, including 50,272 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 0.81 (50272 hom., cov: 31)
• Consequence: CTLA4 ENST00000696479.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.902 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.-24C>A		5_prime_UTR_variant	1/5

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123450 AN: 151974 Hom.: 50226 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.813

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

GnomAD4 genome AF: 0.812 AC: 123552 AN: 152092 Hom.: 50272 Cov.: 31 AF XY: 0.815 AC XY: 60613 AN XY: 74346

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.814

Alfa AF: 0.812 Hom.: 64651

Bravo AF: 0.810

Asia WGS AF: 0.906 AC: 3149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2162610; hg19: chr2-204718729;