rs9938630

chr16-29825787-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005115.5(MVP):c.-35-4728C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,092 control chromosomes in the GnomAD database, including 5,442 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 (5442 hom., cov: 31)
• Consequence: MVP NM_005115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MVP	NM_005115.5	c.-35-4728C>T		intron_variant		ENST00000357402.10
MVP	NM_017458.3	c.-76-4687C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MVP	ENST00000357402.10	c.-35-4728C>T		intron_variant		1	NM_005115.5	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34302 AN: 151974 Hom.: 5413 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.226 AC: 34381 AN: 152092 Hom.: 5442 Cov.: 31 AF XY: 0.220 AC XY: 16375 AN XY: 74360

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0899

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.181

Alfa AF: 0.212 Hom.: 1047

Bravo AF: 0.238

Asia WGS AF: 0.105 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.13
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9938630; hg19: chr16-29837108;