rs11571319

Variant names:

• chr2-203874215-G-A
• rs11571319
• NM_005214.5:c.*1403G>A

Variant summary

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

The NM_005214.5(CTLA4):​c.*1403G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,198 control chromosomes in the GnomAD database, including 2,121 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 (2121 hom., cov: 33)
• Consequence: CTLA4 NM_005214.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTLA4	NM_005214.5	c.*1403G>A		downstream_gene_variant		ENST00000648405.2	NP_005205.2
CTLA4	NM_001037631.3	c.*1440G>A		downstream_gene_variant			NP_001032720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000648405.2	c.*1403G>A		downstream_gene_variant			NM_005214.5	ENSP00000497102.1
CTLA4	ENST00000696479.1	c.*1403G>A		downstream_gene_variant				ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 25012 AN: 152080 Hom.: 2113 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.165 AC: 25039 AN: 152198 Hom.: 2121 Cov.: 33 AF XY: 0.162 AC XY: 12041 AN XY: 74416

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.164

Alfa AF: 0.165 Hom.: 421

Bravo AF: 0.165

Asia WGS AF: 0.0890 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11571319; hg19: chr2-204738938;