rs3815824

Positions:

• chr16-29841539-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.1192-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,518,102 control chromosomes in the GnomAD database, including 16,509 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 0.16 (2157 hom., cov: 31)
  • Exomes 𝑓: 0.14 (14352 hom.)
• Consequence: MVP NM_005115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771

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 (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 = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVP	NM_005115.5	c.1192-57C>T		intron_variant		ENST00000357402.10	NP_005106.2
MVP	NM_017458.3	c.1192-57C>T		intron_variant			NP_059447.2
MVP	NM_001293204.1	c.1192-57C>T		intron_variant			NP_001280133.1
MVP	NM_001293205.1	c.1192-57C>T		intron_variant			NP_001280134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVP	ENST00000357402.10	c.1192-57C>T		intron_variant		1	NM_005115.5	ENSP00000349977.5
MVP	ENST00000395353.5	c.1192-57C>T		intron_variant		5		ENSP00000378760.1
MVP	ENST00000563558.5	c.379-57C>T		intron_variant		4		ENSP00000454825.1
MVP	ENST00000568068.1	n.367-57C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24391 AN: 151836 Hom.: 2145 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.141 AC: 192557 AN: 1366148 Hom.: 14352 AF XY: 0.141 AC XY: 94015 AN XY: 669068

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0756

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.0379

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.161 AC: 24445 AN: 151954 Hom.: 2157 Cov.: 31 AF XY: 0.156 AC XY: 11591 AN XY: 74278

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.138

Alfa AF: 0.159 Hom.: 299

Bravo AF: 0.163

Asia WGS AF: 0.0700 AC: 244 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	0.33
DANN	Benign	0.61

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: rs3815824; hg19: chr16-29852860;