rs4788186

Variant names:

• chr16-29829904-A-G
• rs4788186
• NM_005115.5:c.-35-611A>G

Variant summary

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

The NM_005115.5(MVP):​c.-35-611A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,408 control chromosomes in the GnomAD database, including 35,265 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 0.66 (35208 hom., cov: 32)
  • Exomes 𝑓: 0.52 (57 hom.)
• Consequence: MVP NM_005115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVP	NM_005115.5	c.-35-611A>G		intron_variant	Intron 1 of 14	ENST00000357402.10	NP_005106.2
MVP	NM_017458.3	c.-76-570A>G		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.-35-611A>G		intron_variant	Intron 1 of 14	1	NM_005115.5	ENSP00000349977.5
ENSG00000281348	ENST00000562285.1	n.*149-570A>G		intron_variant	Intron 2 of 2	2		ENSP00000457363.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99651 AN: 151936 Hom.: 35161 Cov.: 32

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.523 AC: 185 AN: 354 Hom.: 57 Cov.: 0 AF XY: 0.521 AC XY: 98 AN XY: 188

Gnomad4 AMR exome AF: 0.321

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.656 AC: 99743 AN: 152054 Hom.: 35208 Cov.: 32 AF XY: 0.645 AC XY: 47964 AN XY: 74322

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.605

Alfa AF: 0.600 Hom.: 36762

Bravo AF: 0.663

Asia WGS AF: 0.331 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.35

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: rs4788186; hg19: chr16-29841225;