NM_024626.4:c.33-9387C>A

Variant names:

• chr1-117179558-G-T
• rs4376721
• NM_024626.4:c.33-9387C>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.33-9387C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,192 control chromosomes in the GnomAD database, including 47,689 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 0.78 (47689 hom., cov: 32)
• Consequence: VTCN1 NM_024626.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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.33-9387C>A		intron	N/A	NP_078902.2
	VTCN1	NM_001253849.2		c.-253-9387C>A		intron	N/A	NP_001240778.1
	VTCN1	NM_001253850.2		c.33-9387C>A		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.33-9387C>A		intron	N/A	ENSP00000358470.3
	VTCN1	ENST00000539893.5	TSL:2	c.-253-9387C>A		intron	N/A	ENSP00000444724.1
	VTCN1	ENST00000328189.7	TSL:5	c.33-9387C>A		intron	N/A	ENSP00000328168.3

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119124 AN: 152074 Hom.: 47635 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.783 AC: 119236 AN: 152192 Hom.: 47689 Cov.: 32 AF XY: 0.787 AC XY: 58537 AN XY: 74412

African (AFR) AF: 0.926 AC: 38480 AN: 41542

American (AMR) AF: 0.792 AC: 12115 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2314 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5141 AN: 5174

South Asian (SAS) AF: 0.824 AC: 3977 AN: 4826

European-Finnish (FIN) AF: 0.741 AC: 7842 AN: 10578

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47178 AN: 67980

Other (OTH) AF: 0.746 AC: 1578 AN: 2116

Alfa AF: 0.733 Hom.: 28437

Bravo AF: 0.792

Asia WGS AF: 0.916 AC: 3183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.86
DANN	Benign	0.54
PhyloP100		-0.083
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: rs4376721; hg19: chr1-117722180;