1-117203951-C-T

Variant names:

• chr1-117203951-C-T
• rs10923223
• NM_024626.4:c.32+6873G>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.32+6873G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 210,140 control chromosomes in the GnomAD database, including 64,459 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 0.76 (44605 hom., cov: 31)
  • Exomes 𝑓: 0.82 (19854 hom.)
• Consequence: VTCN1 NM_024626.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTCN1	NM_024626.4	c.32+6873G>A		intron_variant	Intron 1 of 5	ENST00000369458.8	NP_078902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTCN1	ENST00000369458.8	c.32+6873G>A		intron_variant	Intron 1 of 5	1	NM_024626.4	ENSP00000358470.3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115345 AN: 151948 Hom.: 44580 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.764

GnomAD4 exome AF: 0.824 AC: 47846 AN: 58074 Hom.: 19854 AF XY: 0.824 AC XY: 23319 AN XY: 28300

African (AFR) AF: 0.597 AC: 584 AN: 978

American (AMR) AF: 0.706 AC: 48 AN: 68

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 275 AN: 356

East Asian (EAS) AF: 0.558 AC: 126 AN: 226

South Asian (SAS) AF: 0.703 AC: 801 AN: 1140

European-Finnish (FIN) AF: 0.821 AC: 23 AN: 28

Middle Eastern (MID) AF: 0.660 AC: 99 AN: 150

European-Non Finnish (NFE) AF: 0.835 AC: 44418 AN: 53204

Other (OTH) AF: 0.765 AC: 1472 AN: 1924

GnomAD4 genome AF: 0.759 AC: 115409 AN: 152066 Hom.: 44605 Cov.: 31 AF XY: 0.758 AC XY: 56385 AN XY: 74346

African (AFR) AF: 0.611 AC: 25322 AN: 41414

American (AMR) AF: 0.778 AC: 11879 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2733 AN: 3468

East Asian (EAS) AF: 0.602 AC: 3114 AN: 5176

South Asian (SAS) AF: 0.722 AC: 3475 AN: 4814

European-Finnish (FIN) AF: 0.864 AC: 9155 AN: 10596

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57117 AN: 68006

Other (OTH) AF: 0.767 AC: 1619 AN: 2112

Alfa AF: 0.780 Hom.: 7062

Bravo AF: 0.745

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.040
DANN	Benign	0.52
PhyloP100		-1.2
PromoterAI		-0.0042	Neutral
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: rs10923223; hg19: chr1-117746573;