chr2-203866178-T-C

Variant names:

• chr2-203866178-T-C
• rs11571315
• ENST00000696479.1:c.48-1740T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696479.1(CTLA4):​c.48-1740T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,016 control chromosomes in the GnomAD database, including 23,130 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 0.55 (23130 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 40 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000696479.1	c.48-1740T>C		intron_variant	Intron 1 of 4			ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83040 AN: 151898 Hom.: 23132 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.546 AC: 83065 AN: 152016 Hom.: 23130 Cov.: 32 AF XY: 0.541 AC XY: 40194 AN XY: 74284

African (AFR) AF: 0.498 AC: 20661 AN: 41476

American (AMR) AF: 0.559 AC: 8535 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2300 AN: 3466

East Asian (EAS) AF: 0.354 AC: 1826 AN: 5164

South Asian (SAS) AF: 0.654 AC: 3150 AN: 4816

European-Finnish (FIN) AF: 0.462 AC: 4872 AN: 10550

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39742 AN: 67960

Other (OTH) AF: 0.598 AC: 1264 AN: 2114

Alfa AF: 0.582 Hom.: 74464

Bravo AF: 0.548

Asia WGS AF: 0.532 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.74
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs11571315; hg19: chr2-204730901;