rs231779

chr2-203869764-C-T

Variant summary

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

The NM_005214.5(CTLA4):c.110-822C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,892 control chromosomes in the GnomAD database, including 13,184 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 0.41 (13184 hom., cov: 31)
• Consequence: CTLA4 NM_005214.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTLA4	NM_005214.5	c.110-822C>T		intron_variant		ENST00000648405.2
CTLA4	NM_001037631.3	c.110-822C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTLA4	ENST00000648405.2	c.110-822C>T		intron_variant			NM_005214.5	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62225 AN: 151774 Hom.: 13165 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.410 AC: 62286 AN: 151892 Hom.: 13184 Cov.: 31 AF XY: 0.416 AC XY: 30860 AN XY: 74240

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.365

Alfa AF: 0.381 Hom.: 11694

Bravo AF: 0.408

Asia WGS AF: 0.445 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.3
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs231779; hg19: chr2-204734487;