rs736611

Variant names:

• chr2-203865742-C-T
• rs736611
• ENST00000696479.1:c.48-2176C>T

Variant summary

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

The ENST00000696479.1(CTLA4):​c.48-2176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,128 control chromosomes in the GnomAD database, including 24,165 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 0.56 (24165 hom., cov: 33)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 10 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=-0.94).
• 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.48-2176C>T		intron_variant	Intron 1 of 4			ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 85025 AN: 152010 Hom.: 24156 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.559 AC: 85068 AN: 152128 Hom.: 24165 Cov.: 33 AF XY: 0.553 AC XY: 41138 AN XY: 74342

African (AFR) AF: 0.541 AC: 22444 AN: 41496

American (AMR) AF: 0.564 AC: 8620 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2368 AN: 3472

East Asian (EAS) AF: 0.354 AC: 1832 AN: 5178

South Asian (SAS) AF: 0.654 AC: 3156 AN: 4826

European-Finnish (FIN) AF: 0.461 AC: 4874 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39775 AN: 67994

Other (OTH) AF: 0.607 AC: 1282 AN: 2112

Alfa AF: 0.558 Hom.: 3360

Bravo AF: 0.562

Asia WGS AF: 0.541 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.044
DANN	Benign	0.58
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs736611; hg19: chr2-204730465;