9-126422030-G-A

Variant names:

• chr9-126422030-G-A
• rs887659
• NM_033446.3:c.757+82G>A

Variant summary

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

The NM_033446.3(MVB12B):​c.757+82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 982,800 control chromosomes in the GnomAD database, including 103,993 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 0.47 (17001 hom., cov: 30)
  • Exomes 𝑓: 0.45 (86992 hom.)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	NM_033446.3	MANE Select	c.757+82G>A		intron	N/A	NP_258257.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.757+82G>A		intron	N/A	ENSP00000354772.3
	MVB12B	ENST00000470567.5	TSL:5	n.153+82G>A		intron	N/A
	MVB12B	ENST00000489570.1	TSL:3	n.95+82G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71311 AN: 151682 Hom.: 16984 Cov.: 30

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.453 AC: 376479 AN: 831000 Hom.: 86992 AF XY: 0.458 AC XY: 200155 AN XY: 436668

African (AFR) AF: 0.497 AC: 10706 AN: 21554

American (AMR) AF: 0.468 AC: 19633 AN: 41986

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 8984 AN: 21782

East Asian (EAS) AF: 0.294 AC: 10748 AN: 36536

South Asian (SAS) AF: 0.553 AC: 40312 AN: 72940

European-Finnish (FIN) AF: 0.482 AC: 20233 AN: 41940

Middle Eastern (MID) AF: 0.475 AC: 2148 AN: 4522

European-Non Finnish (NFE) AF: 0.448 AC: 246231 AN: 549582

Other (OTH) AF: 0.435 AC: 17484 AN: 40158

GnomAD4 genome AF: 0.470 AC: 71361 AN: 151800 Hom.: 17001 Cov.: 30 AF XY: 0.472 AC XY: 34987 AN XY: 74198

African (AFR) AF: 0.503 AC: 20802 AN: 41384

American (AMR) AF: 0.484 AC: 7387 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1407 AN: 3472

East Asian (EAS) AF: 0.289 AC: 1488 AN: 5142

South Asian (SAS) AF: 0.540 AC: 2599 AN: 4810

European-Finnish (FIN) AF: 0.479 AC: 5056 AN: 10562

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31127 AN: 67852

Other (OTH) AF: 0.438 AC: 922 AN: 2104

Alfa AF: 0.451 Hom.: 66724

Bravo AF: 0.462

Asia WGS AF: 0.411 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.036
DANN	Benign	0.70
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs887659; hg19: chr9-129184309; COSMIC: COSV63257236; COSMIC: COSV63257236;