rs4553808

Variant names:

• chr2-203866282-A-G
• rs4553808
• ENST00000696479.1:c.48-1636A>G

Your query was ambiguous. Multiple possible variants found:

• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000696479.1	c.48-1636A>G		intron_variant	Intron 1 of 4			ENSP00000512655.1

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;