rs733618

Positions:

• chr2-203866221-T-C

Variant summary

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

The ENST00000696479.1(CTLA4):​c.48-1697T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,230 control chromosomes in the GnomAD database, including 1,131 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 0.10 (1131 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 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.48-1697T>C		intron_variant				ENSP00000512655

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15961 AN: 152114 Hom.: 1129 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0990

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

GnomAD4 genome AF: 0.105 AC: 15976 AN: 152230 Hom.: 1131 Cov.: 32 AF XY: 0.107 AC XY: 7938 AN XY: 74448

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0930

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.0975

Alfa AF: 0.0828 Hom.: 835

Bravo AF: 0.110

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
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: rs733618; hg19: chr2-204730944;