2-203868865-T-C

Position:

• chr2-203868865-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005214.5(CTLA4):​c.109+814T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,170 control chromosomes in the GnomAD database, including 53,168 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 0.83 (53168 hom., cov: 31)
• Consequence: CTLA4 NM_005214.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTLA4	NM_005214.5	c.109+814T>C		intron_variant		ENST00000648405.2	NP_005205.2
CTLA4	NM_001037631.3	c.109+814T>C		intron_variant			NP_001032720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000648405.2	c.109+814T>C		intron_variant			NM_005214.5	ENSP00000497102	P1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126918 AN: 152052 Hom.: 53139 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.835 AC: 126990 AN: 152170 Hom.: 53168 Cov.: 31 AF XY: 0.837 AC XY: 62281 AN XY: 74400

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.841

Alfa AF: 0.839 Hom.: 8522

Bravo AF: 0.831

Asia WGS AF: 0.907 AC: 3152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.89

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: rs231777; hg19: chr2-204733588;