chr2-203854006-C-A

Variant names:

• chr2-203854006-C-A
• rs2162610
• ENST00000696479.1:c.-24C>A

Variant summary

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

The ENST00000696479.1(CTLA4):​c.-24C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,092 control chromosomes in the GnomAD database, including 50,272 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 0.81 (50272 hom., cov: 31)
• Consequence: CTLA4 ENST00000696479.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 14 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.902 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.-24C>A		5_prime_UTR_variant	Exon 1 of 5			ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123450 AN: 151974 Hom.: 50226 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.813

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

GnomAD4 genome AF: 0.812 AC: 123552 AN: 152092 Hom.: 50272 Cov.: 31 AF XY: 0.815 AC XY: 60613 AN XY: 74346

African (AFR) AF: 0.783 AC: 32482 AN: 41470

American (AMR) AF: 0.840 AC: 12840 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2848 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4579 AN: 5158

South Asian (SAS) AF: 0.925 AC: 4455 AN: 4818

European-Finnish (FIN) AF: 0.824 AC: 8711 AN: 10574

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54910 AN: 67996

Other (OTH) AF: 0.814 AC: 1717 AN: 2110

Alfa AF: 0.812 Hom.: 82439

Bravo AF: 0.810

Asia WGS AF: 0.906 AC: 3149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.54
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs2162610; hg19: chr2-204718729;