rs2358820

Variant names:

• chr1-117169289-G-A
• rs2358820
• NM_024626.4:c.97+818C>T

Variant summary

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

The NM_024626.4(VTCN1):​c.97+818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 152,270 control chromosomes in the GnomAD database, including 274 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 0.054 (274 hom., cov: 32)
• Consequence: VTCN1 NM_024626.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77
• Publications: 5 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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024626.4. 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
	VTCN1	NM_024626.4	MANE Select	c.97+818C>T		intron	N/A	NP_078902.2
	VTCN1	NM_001253849.2		c.-189+818C>T		intron	N/A	NP_001240778.1
	VTCN1	NM_001253850.2		c.97+818C>T		intron	N/A	NP_001240779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTCN1	ENST00000369458.8	TSL:1 MANE Select	c.97+818C>T		intron	N/A	ENSP00000358470.3
	VTCN1	ENST00000359008.8	TSL:5	c.106+818C>T		intron	N/A	ENSP00000351899.4
	VTCN1	ENST00000539893.5	TSL:2	c.-189+818C>T		intron	N/A	ENSP00000444724.1

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8240 AN: 152152 Hom.: 272 Cov.: 32

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0831

Gnomad FIN AF: 0.0396

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0650

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

GnomAD4 genome AF: 0.0541 AC: 8245 AN: 152270 Hom.: 274 Cov.: 32 AF XY: 0.0523 AC XY: 3891 AN XY: 74462

African (AFR) AF: 0.0275 AC: 1144 AN: 41556

American (AMR) AF: 0.0620 AC: 948 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 198 AN: 3470

East Asian (EAS) AF: 0.0179 AC: 93 AN: 5182

South Asian (SAS) AF: 0.0827 AC: 399 AN: 4824

European-Finnish (FIN) AF: 0.0396 AC: 420 AN: 10602

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0716 AC: 4868 AN: 68014

Other (OTH) AF: 0.0700 AC: 148 AN: 2114

Alfa AF: 0.0613 Hom.: 44

Bravo AF: 0.0538

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.65
PhyloP100		-3.8
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: rs2358820; hg19: chr1-117711911;