rs4553808

Positions:

• chr2-203866282-A-G
• chr2-203866282-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696479.1(CTLA4):​c.48-1636A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,972 control chromosomes in the GnomAD database, including 2,040 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 0.16 (2040 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000696479.1	c.48-1636A>G		intron_variant				ENSP00000512655

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24539 AN: 151854 Hom.: 2036 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.162 AC: 24556 AN: 151972 Hom.: 2040 Cov.: 32 AF XY: 0.159 AC XY: 11804 AN XY: 74254

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.164

Alfa AF: 0.121 Hom.: 280

Bravo AF: 0.162

Asia WGS AF: 0.0880 AC: 310 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4553808; hg19: chr2-204731005;