9-126484208-A-C

Variant names:

• chr9-126484208-A-C
• rs2286885
• NM_033446.3:c.873+176A>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.873+176A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,144 control chromosomes in the GnomAD database, including 13,057 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 (13057 hom., cov: 33)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390
• Publications: 15 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=-0.96).
• 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 rank	MANE	Protein	UniProt
MVB12B	NM_033446.3	c.873+176A>C		intron_variant	Intron 9 of 9	ENST00000361171.8	NP_258257.1
MVB12B	XM_005252297.1	c.828+176A>C		intron_variant	Intron 9 of 9		XP_005252354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVB12B	ENST00000361171.8	c.873+176A>C		intron_variant	Intron 9 of 9	2	NM_033446.3	ENSP00000354772.3
MVB12B	ENST00000485886.1	n.672+176A>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60941 AN: 152026 Hom.: 13048 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 60969 AN: 152144 Hom.: 13057 Cov.: 33 AF XY: 0.401 AC XY: 29848 AN XY: 74384

African (AFR) AF: 0.255 AC: 10572 AN: 41516

American (AMR) AF: 0.431 AC: 6594 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3658 AN: 5168

South Asian (SAS) AF: 0.395 AC: 1908 AN: 4826

European-Finnish (FIN) AF: 0.456 AC: 4825 AN: 10578

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

European-Non Finnish (NFE) AF: 0.446 AC: 30305 AN: 67984

Other (OTH) AF: 0.438 AC: 926 AN: 2114

Alfa AF: 0.434 Hom.: 7642

Bravo AF: 0.403

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	-0.96
CADD	Benign	7.2
DANN	Benign	0.37
PhyloP100		0.39
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

Other links and lift over

dbSNP: rs2286885; hg19: chr9-129246487;