rs3087243

Variant names:

• chr2-203874196-G-A
• rs3087243
• NM_005214.5:c.*1384G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-203874196-G-A
• chr2-203874196-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005214.5(CTLA4):​c.*1384G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,058 control chromosomes in the GnomAD database, including 11,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.37 (11260 hom., cov: 32)
• Consequence: CTLA4 NM_005214.5 downstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:2
• Conservation: PhyloP100: -0.151
• Publications: 559 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-203874196-G-A is Benign according to our data. Variant chr2-203874196-G-A is described in ClinVar as Benign. ClinVar VariationId is 16922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTLA4	NM_005214.5	c.*1384G>A		downstream_gene_variant		ENST00000648405.2	NP_005205.2
CTLA4	NM_001037631.3	c.*1421G>A		downstream_gene_variant			NP_001032720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000648405.2	c.*1384G>A		downstream_gene_variant			NM_005214.5	ENSP00000497102.1
CTLA4	ENST00000696479.1	c.*1384G>A		downstream_gene_variant				ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56263 AN: 151940 Hom.: 11262 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.370 AC: 56261 AN: 152058 Hom.: 11260 Cov.: 32 AF XY: 0.368 AC XY: 27352 AN XY: 74320

African (AFR) AF: 0.228 AC: 9461 AN: 41466

American (AMR) AF: 0.412 AC: 6298 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1737 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5164

South Asian (SAS) AF: 0.606 AC: 2922 AN: 4820

European-Finnish (FIN) AF: 0.314 AC: 3320 AN: 10568

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29810 AN: 67978

Other (OTH) AF: 0.430 AC: 907 AN: 2110

Alfa AF: 0.422 Hom.: 55410

Bravo AF: 0.366

Asia WGS AF: 0.444 AC: 1542 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

chronic fatigue syndrome with infection-triggered onset Benign:1

Feb 10, 2020

Institute for Medical Immunology, Charité - Universitätsmedizin Berlin

Significance: protective

Review Status: no assertion criteria provided

Collection Method: case-control

G allele is associated with chronic fatigue syndrome with infection-triggered onset (OR 1.53 [CI 1.17-2.03], p = 0,001) -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hashimoto thyroiditis, susceptibility to Other:1

Oct 17, 2011

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Celiac disease, susceptibility to, 3 Other:1

Sep 01, 2004

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs3087243; hg19: chr2-204738919;