rs11571316

chr2-203866366-G-Achr2-203866366-G-Cchr2-203866366-G-T

Variant summary

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

The ENST00000696479.1(CTLA4):c.48-1552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,986 control chromosomes in the GnomAD database, including 10,136 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 0.35 (10136 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 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.48-1552G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53518 AN: 151870 Hom.: 10141 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.352 AC: 53514 AN: 151986 Hom.: 10136 Cov.: 32 AF XY: 0.351 AC XY: 26061 AN XY: 74284

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.408

Alfa AF: 0.318 Hom.: 2080

Bravo AF: 0.348

Asia WGS AF: 0.437 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.33
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11571316; hg19: chr2-204731089;