rs2286886

Variant names:

• chr9-126483898-T-C
• rs2286886
• NM_033446.3:c.814-75T>C

Variant summary

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

The NM_033446.3(MVB12B):​c.814-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,479,746 control chromosomes in the GnomAD database, including 152,546 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 0.40 (13165 hom., cov: 33)
  • Exomes 𝑓: 0.45 (139381 hom.)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.866
• Publications: 10 publications found

Genes affected

MVB12B (HGNC:23368): (multivesicular body subunit 12B) The protein encoded by this gene is a component of the ESCRT-I complex, a heterotetramer, which mediates the sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle. ESCRT-I complex plays an essential role in HIV budding and endosomal protein sorting. Depletion and overexpression of this and related protein (MVB12A) inhibit HIV-1 infectivity and induce unusual viral assembly defects, indicating a role for MVB12 subunits in regulating ESCRT-mediated virus budding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	NM_033446.3	MANE Select	c.814-75T>C		intron	N/A	NP_258257.1	Q9H7P6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.814-75T>C		intron	N/A	ENSP00000354772.3	Q9H7P6-1
	MVB12B	ENST00000885963.1		c.949-75T>C		intron	N/A	ENSP00000556022.1
	MVB12B	ENST00000885962.1		c.865-75T>C		intron	N/A	ENSP00000556021.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61344 AN: 151960 Hom.: 13156 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.453 AC: 601507 AN: 1327666 Hom.: 139381 AF XY: 0.450 AC XY: 299688 AN XY: 666476

African (AFR) AF: 0.259 AC: 8007 AN: 30966

American (AMR) AF: 0.484 AC: 21220 AN: 43848

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 12077 AN: 24622

East Asian (EAS) AF: 0.706 AC: 27552 AN: 39000

South Asian (SAS) AF: 0.376 AC: 30790 AN: 81896

European-Finnish (FIN) AF: 0.443 AC: 23352 AN: 52764

Middle Eastern (MID) AF: 0.400 AC: 2193 AN: 5484

European-Non Finnish (NFE) AF: 0.453 AC: 450098 AN: 993236

Other (OTH) AF: 0.469 AC: 26218 AN: 55850

GnomAD4 genome AF: 0.404 AC: 61373 AN: 152080 Hom.: 13165 Cov.: 33 AF XY: 0.404 AC XY: 30046 AN XY: 74370

African (AFR) AF: 0.265 AC: 11006 AN: 41482

American (AMR) AF: 0.432 AC: 6607 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1716 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3648 AN: 5152

South Asian (SAS) AF: 0.395 AC: 1907 AN: 4822

European-Finnish (FIN) AF: 0.456 AC: 4820 AN: 10578

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30255 AN: 67978

Other (OTH) AF: 0.438 AC: 924 AN: 2108

Alfa AF: 0.438 Hom.: 56686

Bravo AF: 0.406

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.48
PhyloP100		-0.87
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2286886;

hg19: chr9-129246177;

COSMIC: COSV63260588;