rs2286886

Positions:

• chr9-126483898-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MVB12B	NM_033446.3	c.814-75T>C		intron_variant		ENST00000361171.8
MVB12B	XM_005252297.1	c.769-75T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MVB12B	ENST00000361171.8	c.814-75T>C		intron_variant		2	NM_033446.3	P1
MVB12B	ENST00000485886.1	n.613-75T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.706

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.469

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

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.438

Alfa AF: 0.446 Hom.: 24819

Bravo AF: 0.406

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs2286886; hg19: chr9-129246177; COSMIC: COSV63260588;