rs2358817

Variant names:

• chr1-117148136-C-T
• rs2358817
• NM_024626.4:c.725-354G>A

Variant summary

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

The NM_024626.4(VTCN1):​c.725-354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,178 control chromosomes in the GnomAD database, including 3,739 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 0.17 (3739 hom., cov: 32)
• Consequence: VTCN1 NM_024626.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 9 publications found

Genes affected

VTCN1 (HGNC:28873): (V-set domain containing T cell activation inhibitor 1) This gene encodes a protein belonging to the B7 costimulatory protein family. Proteins in this family are present on the surface of antigen-presenting cells and interact with ligand bound to receptors on the surface of T cells. Studies have shown that high levels of the encoded protein has been correlated with tumor progression. A pseudogene of this gene is located on chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTCN1	NM_024626.4	c.725-354G>A		intron_variant	Intron 4 of 5	ENST00000369458.8	NP_078902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTCN1	ENST00000369458.8	c.725-354G>A		intron_variant	Intron 4 of 5	1	NM_024626.4	ENSP00000358470.3
VTCN1	ENST00000359008.8	c.734-354G>A		intron_variant	Intron 4 of 5	5		ENSP00000351899.4
VTCN1	ENST00000539893.5	c.440-354G>A		intron_variant	Intron 4 of 5	2		ENSP00000444724.1
VTCN1	ENST00000328189.7	c.377-354G>A		intron_variant	Intron 3 of 4	5		ENSP00000328168.3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25539 AN: 152060 Hom.: 3722 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.168 AC: 25598 AN: 152178 Hom.: 3739 Cov.: 32 AF XY: 0.163 AC XY: 12123 AN XY: 74420

African (AFR) AF: 0.399 AC: 16534 AN: 41470

American (AMR) AF: 0.103 AC: 1578 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 259 AN: 3470

East Asian (EAS) AF: 0.0971 AC: 503 AN: 5178

South Asian (SAS) AF: 0.133 AC: 641 AN: 4822

European-Finnish (FIN) AF: 0.0407 AC: 432 AN: 10616

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5274 AN: 68008

Other (OTH) AF: 0.153 AC: 323 AN: 2114

Alfa AF: 0.108 Hom.: 1944

Bravo AF: 0.181

Asia WGS AF: 0.146 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.69
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2358817; hg19: chr1-117690758;