2-203866366-G-A

Variant names:

• chr2-203866366-G-A
• rs11571316
• ENST00000696479.1:c.48-1552G>A

Variant summary

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

The ENST00000696479.1(CTLA4):​c.48-1552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,986 control chromosomes in the GnomAD database, including 10,136 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. The gene CTLA4 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.35 (10136 hom., cov: 32)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 66 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Specifications for CTLA4 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 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.48-1552G>A		intron	N/A	ENSP00000512655.1	A0A8Q3SIR7

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53518 AN: 151870 Hom.: 10141 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.352 AC: 53514 AN: 151986 Hom.: 10136 Cov.: 32 AF XY: 0.351 AC XY: 26061 AN XY: 74284

African (AFR) AF: 0.224 AC: 9284 AN: 41446

American (AMR) AF: 0.397 AC: 6064 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1678 AN: 3472

East Asian (EAS) AF: 0.246 AC: 1269 AN: 5160

South Asian (SAS) AF: 0.583 AC: 2811 AN: 4822

European-Finnish (FIN) AF: 0.303 AC: 3196 AN: 10546

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27827 AN: 67966

Other (OTH) AF: 0.408 AC: 861 AN: 2108

Alfa AF: 0.387 Hom.: 16445

Bravo AF: 0.348

Asia WGS AF: 0.437 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.53
PhyloP100		-0.14

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11571316;

hg19: chr2-204731089;