Genetic Variant VTCN1:c.446-46C>T (chr1-117153415-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024626.4(VTCN1):c.446-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,555,558 control chromosomes in the GnomAD database, including 19,742 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 0.23 ( 8185 hom., cov: 31)

Exomes 𝑓: 0.095 ( 11557 hom. )

Consequence

VTCN1
NM_024626.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.364

Publications

8 publications found

Variant links:

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]

VTCN1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTCN1	NM_024626.4 link	c.446-46C>T		intron_variant	Intron 3 of 5	ENST00000369458.8	NP_078902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTCN1	ENST00000369458.8 link	c.446-46C>T		intron_variant	Intron 3 of 5	1	NM_024626.4	ENSP00000358470.3		Q7Z7D3-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34505

AN:

151454

Hom.:

8147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0750

Gnomad EAS

AF:

0.0969

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.0409

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0784

Gnomad OTH

AF:

0.193

GnomAD2 exomes

AF:

0.121

AC:

25307

AN:

209030

AF XY:

0.114

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.0713

Gnomad ASJ exome

AF:

0.0794

Gnomad EAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0421

Gnomad NFE exome

AF:

0.0763

Gnomad OTH exome

AF:

0.0942

GnomAD4 exome

AF:

0.0949

AC:

133270

AN:

1403998

Hom.:

11557

Cov.:

AF XY:

0.0944

AC XY:

65316

AN XY:

691902

show subpopulations

African (AFR)

AF:

0.627

AC:

19895

AN:

31706

American (AMR)

AF:

0.0774

AC:

2876

AN:

37140

Ashkenazi Jewish (ASJ)

AF:

0.0765

AC:

1722

AN:

22496

East Asian (EAS)

AF:

0.105

AC:

4089

AN:

38924

South Asian (SAS)

AF:

0.128

AC:

9935

AN:

77876

European-Finnish (FIN)

AF:

0.0400

AC:

2055

AN:

51400

Middle Eastern (MID)

AF:

0.124

AC:

674

AN:

5438

European-Non Finnish (NFE)

AF:

0.0788

AC:

85177

AN:

1081228

Other (OTH)

AF:

0.118

AC:

6847

AN:

57790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

5687

11374

17060

22747

28434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3580

7160

10740

14320

17900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.228

AC:

34599

AN:

151560

Hom.:

8185

Cov.:

AF XY:

0.222

AC XY:

16403

AN XY:

74006

show subpopulations

African (AFR)

AF:

0.610

AC:

25113

AN:

41162

American (AMR)

AF:

0.122

AC:

1856

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0750

AC:

260

AN:

3466

East Asian (EAS)

AF:

0.0967

AC:

498

AN:

5148

South Asian (SAS)

AF:

0.134

AC:

643

AN:

4796

European-Finnish (FIN)

AF:

0.0409

AC:

428

AN:

10462

Middle Eastern (MID)

AF:

0.151

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0784

AC:

5326

AN:

67956

Other (OTH)

AF:

0.198

AC:

416

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

900

1799

2699

3598

4498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.135

Hom.:

2656

Bravo

AF:

0.250

Asia WGS

AF:

0.162

AC:

563

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

1.4

(source)

DANN

Benign

0.70

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over