NM_005214.5:c.*1353T>C

Variant names:

• chr2-203874165-T-C
• rs34031880
• NM_005214.5:c.*1353T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005214.5(CTLA4):​c.*1353T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 152,352 control chromosomes in the GnomAD database, including 33 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 0.011 (33 hom., cov: 33)
• Consequence: CTLA4 NM_005214.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1738/152352) while in subpopulation AFR AF= 0.0379 (1574/41578). AF 95% confidence interval is 0.0363. There are 33 homozygotes in gnomad4. There are 837 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1738 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTLA4	NM_005214.5	c.*1353T>C		downstream_gene_variant		ENST00000648405.2	NP_005205.2
CTLA4	NM_001037631.3	c.*1390T>C		downstream_gene_variant			NP_001032720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000648405.2	c.*1353T>C		downstream_gene_variant			NM_005214.5	ENSP00000497102.1
CTLA4	ENST00000696479.1	c.*1353T>C		downstream_gene_variant				ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1738 AN: 152234 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0100

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

GnomAD4 genome AF: 0.0114 AC: 1738 AN: 152352 Hom.: 33 Cov.: 33 AF XY: 0.0112 AC XY: 837 AN XY: 74510

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00925 Hom.: 4

Bravo AF: 0.0130

Asia WGS AF: 0.00173 AC: 6 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	7.6
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34031880; hg19: chr2-204738888;