rs4788187

Positions:

• chr16-29834364-T-C

Variant summary

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

The NM_005115.5(MVP):​c.577+298T>C variant causes a intron 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 NM_005115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVP	NM_005115.5	c.577+298T>C		intron_variant		ENST00000357402.10	NP_005106.2
MVP	NM_001293204.1	c.577+298T>C		intron_variant			NP_001280133.1
MVP	NM_001293205.1	c.577+298T>C		intron_variant			NP_001280134.1
MVP	NM_017458.3	c.577+298T>C		intron_variant			NP_059447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10	c.577+298T>C		intron_variant		1	NM_005115.5	ENSP00000349977	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36058 AN: 151958 Hom.: 6155 Cov.: 31

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.: 3 AF XY: 0.144 AC XY: 17591 AN XY: 122236

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.0993

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.0881

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.238 AC: 36140 AN: 152076 Hom.: 6188 Cov.: 31 AF XY: 0.232 AC XY: 17237 AN XY: 74336

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0918

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.193

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
DANN	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs4788187; hg19: chr16-29845685;