rs887659

Positions:

• chr9-126422030-G-A
• chr9-126422030-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVB12B	NM_033446.3	c.757+82G>A		intron_variant		ENST00000361171.8	NP_258257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVB12B	ENST00000361171.8	c.757+82G>A		intron_variant		2	NM_033446.3	ENSP00000354772.3
MVB12B	ENST00000470567.5	n.153+82G>A		intron_variant		5
MVB12B	ENST00000489570.1	n.95+82G>A		intron_variant		3

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

Gnomad4 AFR exome AF: 0.497

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.553

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.435

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

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.438

Alfa AF: 0.448 Hom.: 31070

Bravo AF: 0.462

Asia WGS AF: 0.411 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.036
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs887659; hg19: chr9-129184309; COSMIC: COSV63257236; COSMIC: COSV63257236;