dbSNP rs4788187: MVP:n.950T>C (chr16-29834364-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 ENST00000569612.1(MVP):n.950T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 378,874 control chromosomes in the GnomAD database, including 9,157 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 0.24 ( 6188 hom., cov: 31)

Exomes 𝑓: 0.15 ( 2969 hom. )

Consequence

MVP
ENST00000569612.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0600

Publications

12 publications found

Variant links:

Genes affected

MVP (HGNC:7531): (major vault protein) This gene encodes the major component of the vault complex. Vaults are multi-subunit ribonucleoprotein structures that may be involved in nucleo-cytoplasmic transport. The encoded protein may play a role in multiple cellular processes by regulating the MAP kinase, JAK/STAT and phosphoinositide 3-kinase/Akt signaling pathways. The encoded protein also plays a role in multidrug resistance, and expression of this gene may be a prognostic marker for several types of cancer. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

MVP links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MVP	NM_005115.5 link	c.577+298T>C	intron_variant	Intron 5 of 14	ENST00000357402.10	NP_005106.2
MVP	NM_017458.3 link	c.577+298T>C	intron_variant	Intron 5 of 14		NP_059447.2
MVP	NM_001293204.1 link	c.577+298T>C	intron_variant	Intron 4 of 13		NP_001280133.1
MVP	NM_001293205.1 link	c.577+298T>C	intron_variant	Intron 4 of 12		NP_001280134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10 link	c.577+298T>C		intron_variant	Intron 5 of 14	1	NM_005115.5	ENSP00000349977.5

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36058

AN:

151958

Hom.:

6155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0924

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.138

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.194

GnomAD4 exome

AF:

0.146

AC:

33025

AN:

226798

Hom.:

2969

Cov.:

AF XY:

0.144

AC XY:

17591

AN XY:

122236

show subpopulations

African (AFR)

AF:

0.486

AC:

3096

AN:

6364

American (AMR)

AF:

0.0993

AC:

1105

AN:

11126

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

919

AN:

5960

East Asian (EAS)

AF:

0.0881

AC:

964

AN:

10942

South Asian (SAS)

AF:

0.130

AC:

5346

AN:

41018

European-Finnish (FIN)

AF:

0.123

AC:

1266

AN:

10298

Middle Eastern (MID)

AF:

0.130

AC:

107

AN:

826

European-Non Finnish (NFE)

AF:

0.143

AC:

18448

AN:

128576

Other (OTH)

AF:

0.152

AC:

1774

AN:

11688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1329

2658

3988

5317

6646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<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:

0.238

AC:

36140

AN:

152076

Hom.:

6188

Cov.:

AF XY:

0.232

AC XY:

17237

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.495

AC:

20524

AN:

41450

American (AMR)

AF:

0.132

AC:

2009

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

565

AN:

3470

East Asian (EAS)

AF:

0.0918

AC:

476

AN:

5184

South Asian (SAS)

AF:

0.107

AC:

516

AN:

4828

European-Finnish (FIN)

AF:

0.126

AC:

1335

AN:

10576

Middle Eastern (MID)

AF:

0.145

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.148

AC:

10075

AN:

67982

Other (OTH)

AF:

0.193

AC:

408

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1207

2413

3620

4826

6033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.199

Hom.:

810

Bravo

AF:

0.250

Asia WGS

AF:

0.107

AC:

374

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.6

(source)

DANN

Benign

0.52

PhyloP100

-0.060

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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