rs9938630

Variant names:

• chr16-29825787-C-T
• rs9938630
• NM_005115.5:c.-35-4728C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ENSG00000281348 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MVP	NM_005115.5	c.-35-4728C>T		intron_variant	Intron 1 of 14	ENST00000357402.10	NP_005106.2
MVP	NM_017458.3	c.-76-4687C>T		intron_variant	Intron 1 of 14		NP_059447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10	c.-35-4728C>T		intron_variant	Intron 1 of 14	1	NM_005115.5	ENSP00000349977.5
ENSG00000281348	ENST00000562285.1	n.*149-4687C>T		intron_variant	Intron 2 of 2	2		ENSP00000457363.1

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

African (AFR) AF: 0.461 AC: 19094 AN: 41448

American (AMR) AF: 0.125 AC: 1913 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3470

East Asian (EAS) AF: 0.0899 AC: 465 AN: 5170

South Asian (SAS) AF: 0.103 AC: 498 AN: 4826

European-Finnish (FIN) AF: 0.119 AC: 1257 AN: 10606

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10029 AN: 67978

Other (OTH) AF: 0.181 AC: 382 AN: 2106

Alfa AF: 0.218 Hom.: 1136

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
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9938630; hg19: chr16-29837108;