chr2-203865072-G-A

Variant names:

• chr2-203865072-G-A
• rs1427680
• ENST00000696479.1:c.48-2846G>A

Variant summary

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

The ENST00000696479.1(CTLA4):​c.48-2846G>A 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 152,050 control chromosomes in the GnomAD database, including 24,157 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 (24157 hom., cov: 33)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.635 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTLA4	ENST00000696479.1		c.48-2846G>A		intron	N/A	ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85021 AN: 151932 Hom.: 24148 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.559 AC: 85065 AN: 152050 Hom.: 24157 Cov.: 33 AF XY: 0.554 AC XY: 41175 AN XY: 74336

African (AFR) AF: 0.541 AC: 22424 AN: 41456

American (AMR) AF: 0.565 AC: 8640 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2373 AN: 3472

East Asian (EAS) AF: 0.354 AC: 1830 AN: 5168

South Asian (SAS) AF: 0.654 AC: 3152 AN: 4818

European-Finnish (FIN) AF: 0.463 AC: 4884 AN: 10560

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39764 AN: 67978

Other (OTH) AF: 0.609 AC: 1283 AN: 2108

Alfa AF: 0.587 Hom.: 7695

Bravo AF: 0.562

Asia WGS AF: 0.541 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.64
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs1427680; hg19: chr2-204729795;