Genetic Variant VBP1:c.*334T>C (chrX-155239176-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003372.7(VBP1):c.*334T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 145,308 control chromosomes in the GnomAD database, including 21,520 homozygotes. There are 22,804 hemizygotes in GnomAD. 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 0.55 ( 14276 hom., 18165 hem., cov: 23)

Exomes 𝑓: 0.71 ( 7244 hom. 4639 hem. )

Consequence

VBP1
NM_003372.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.498

Publications

11 publications found

Variant links:

Genes affected

VBP1 (HGNC:12662): (VHL binding protein 1) The protein encoded by this gene interacts with the Von Hippel-Lindau protein to form an intracellular complex. The encoded protein functions as a chaperone protein, and may play a role in the transport of the Von Hippel-Lindau protein from the perinuclear granules to the nucleus or cytoplasm. Alternative splicing and the use of alternate transcription start sites results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Jan 2015]

VBP1 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003372.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VBP1	NM_003372.7	MANE Select	c.*334T>C	3_prime_UTR	Exon 6 of 6	NP_003363.1	P61758-1
VBP1	NM_001303543.1		c.*334T>C	3_prime_UTR	Exon 6 of 6	NP_001290472.1	P61758
VBP1	NM_001303544.1		c.*334T>C	3_prime_UTR	Exon 7 of 7	NP_001290473.1	P61758-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VBP1	ENST00000286428.7	TSL:1 MANE Select	c.*334T>C	3_prime_UTR	Exon 6 of 6	ENSP00000286428.5	P61758-1
VBP1	ENST00000926244.1		c.*334T>C	3_prime_UTR	Exon 6 of 6	ENSP00000596303.1
VBP1	ENST00000971683.1		c.*334T>C	3_prime_UTR	Exon 6 of 6	ENSP00000641742.1

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

60404

AN:

110688

Hom.:

14280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.665

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.725

Gnomad OTH

AF:

0.582

GnomAD4 exome

AF:

0.713

AC:

24644

AN:

34569

Hom.:

7244

Cov.:

AF XY:

0.743

AC XY:

4639

AN XY:

6241

show subpopulations

African (AFR)

AF:

0.147

AC:

133

AN:

904

American (AMR)

AF:

0.616

AC:

833

AN:

1353

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

772

AN:

1075

East Asian (EAS)

AF:

0.812

AC:

1418

AN:

1747

South Asian (SAS)

AF:

0.694

AC:

1189

AN:

1714

European-Finnish (FIN)

AF:

0.749

AC:

1130

AN:

1509

Middle Eastern (MID)

AF:

0.747

AC:

112

AN:

150

European-Non Finnish (NFE)

AF:

0.735

AC:

17372

AN:

23628

Other (OTH)

AF:

0.677

AC:

1685

AN:

2489

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

272

543

815

1086

1358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.545

AC:

60397

AN:

110739

Hom.:

14276

Cov.:

AF XY:

0.551

AC XY:

18165

AN XY:

32969

show subpopulations

African (AFR)

AF:

0.125

AC:

3825

AN:

30684

American (AMR)

AF:

0.610

AC:

6309

AN:

10335

Ashkenazi Jewish (ASJ)

AF:

0.702

AC:

1841

AN:

2624

East Asian (EAS)

AF:

0.729

AC:

2555

AN:

3505

South Asian (SAS)

AF:

0.670

AC:

1763

AN:

2633

European-Finnish (FIN)

AF:

0.751

AC:

4333

AN:

5770

Middle Eastern (MID)

AF:

0.771

AC:

168

AN:

218

European-Non Finnish (NFE)

AF:

0.725

AC:

38282

AN:

52782

Other (OTH)

AF:

0.577

AC:

873

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

706

1412

2118

2824

3530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.658

Hom.:

51447

Bravo

AF:

0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.2

(source)

PhyloP100

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over