chr2-203864430-C-T

Variant names:

• chr2-203864430-C-T
• rs231770
• ENST00000696479.1:c.48-3488C>T

Variant summary

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

The ENST00000696479.1(CTLA4):​c.48-3488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,984 control chromosomes in the GnomAD database, including 13,645 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 0.42 (13645 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 21 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 (EAS) allele frequency at 95% confidence interval = 0.623 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.48-3488C>T		intron	N/A	ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63405 AN: 151866 Hom.: 13628 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.418 AC: 63467 AN: 151984 Hom.: 13645 Cov.: 32 AF XY: 0.423 AC XY: 31415 AN XY: 74288

African (AFR) AF: 0.391 AC: 16208 AN: 41428

American (AMR) AF: 0.428 AC: 6543 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3466

East Asian (EAS) AF: 0.641 AC: 3318 AN: 5174

South Asian (SAS) AF: 0.340 AC: 1636 AN: 4812

European-Finnish (FIN) AF: 0.520 AC: 5481 AN: 10538

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27903 AN: 67964

Other (OTH) AF: 0.379 AC: 800 AN: 2112

Alfa AF: 0.417 Hom.: 18369

Bravo AF: 0.413

Asia WGS AF: 0.448 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.46
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs231770; hg19: chr2-204729153;