ENST00000696479.1:c.48-1122C>T

Variant names:

• chr2-203866796-C-T
• rs16840252
• ENST00000696479.1:c.48-1122C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000696479.1(CTLA4):​c.48-1122C>T 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 152,102 control chromosomes in the GnomAD database, including 2,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2049 hom., cov: 31)
• Consequence: CTLA4 ENST00000696479.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.628
• Publications: 76 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-203866796-C-T is Benign according to our data. Variant chr2-203866796-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTLA4	ENST00000696479.1		c.48-1122C>T		intron	N/A	ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24562 AN: 151984 Hom.: 2044 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0717

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: 0.162 AC: 24576 AN: 152102 Hom.: 2049 Cov.: 31 AF XY: 0.159 AC XY: 11812 AN XY: 74354

African (AFR) AF: 0.165 AC: 6845 AN: 41500

American (AMR) AF: 0.144 AC: 2207 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3470

East Asian (EAS) AF: 0.112 AC: 577 AN: 5168

South Asian (SAS) AF: 0.0715 AC: 344 AN: 4810

European-Finnish (FIN) AF: 0.153 AC: 1622 AN: 10580

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11847 AN: 67984

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.168 Hom.: 3565

Bravo AF: 0.162

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.44
PhyloP100		-0.63

Splicing

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

Other links and lift over

dbSNP: rs16840252; hg19: chr2-204731519;