ENST00000569612.1:n.950T>C

Variant names:

• chr16-29834364-T-C
• rs4788187
• ENST00000569612.1:n.950T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000569612.1(MVP):​n.950T>C variant causes a non coding transcript exon 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 ENST00000569612.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000569612.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVP	NM_005115.5	MANE Select	c.577+298T>C		intron	N/A	NP_005106.2
	MVP	NM_017458.3		c.577+298T>C		intron	N/A	NP_059447.2
	MVP	NM_001293204.1		c.577+298T>C		intron	N/A	NP_001280133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVP	ENST00000569612.1	TSL:1	n.950T>C		non_coding_transcript_exon	Exon 2 of 2
	MVP	ENST00000357402.10	TSL:1 MANE Select	c.577+298T>C		intron	N/A	ENSP00000349977.5
	MVP	ENST00000563123.1	TSL:4	n.*275T>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000458583.1

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

African (AFR) AF: 0.486 AC: 3096 AN: 6364

American (AMR) AF: 0.0993 AC: 1105 AN: 11126

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 919 AN: 5960

East Asian (EAS) AF: 0.0881 AC: 964 AN: 10942

South Asian (SAS) AF: 0.130 AC: 5346 AN: 41018

European-Finnish (FIN) AF: 0.123 AC: 1266 AN: 10298

Middle Eastern (MID) AF: 0.130 AC: 107 AN: 826

European-Non Finnish (NFE) AF: 0.143 AC: 18448 AN: 128576

Other (OTH) AF: 0.152 AC: 1774 AN: 11688

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

African (AFR) AF: 0.495 AC: 20524 AN: 41450

American (AMR) AF: 0.132 AC: 2009 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3470

East Asian (EAS) AF: 0.0918 AC: 476 AN: 5184

South Asian (SAS) AF: 0.107 AC: 516 AN: 4828

European-Finnish (FIN) AF: 0.126 AC: 1335 AN: 10576

Middle Eastern (MID) AF: 0.145 AC: 42 AN: 290

European-Non Finnish (NFE) AF: 0.148 AC: 10075 AN: 67982

Other (OTH) AF: 0.193 AC: 408 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.52
PhyloP100		-0.060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4788187; hg19: chr16-29845685;