rs11571291

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

CTLA4 Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTLA4	ENST00000696479.1		c.47+2333T>C		intron	N/A	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

African (AFR) AF: 0.336 AC: 13923 AN: 41460

American (AMR) AF: 0.415 AC: 6338 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1733 AN: 3468

East Asian (EAS) AF: 0.247 AC: 1280 AN: 5176

South Asian (SAS) AF: 0.589 AC: 2836 AN: 4814

European-Finnish (FIN) AF: 0.309 AC: 3260 AN: 10542

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27924 AN: 67878

Other (OTH) AF: 0.437 AC: 920 AN: 2104

Alfa AF: 0.416 Hom.: 13361

Bravo AF: 0.387

Asia WGS AF: 0.451 AC: 1566 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.55
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs11571291; hg19: chr2-204721132;