chr9-126432494-A-G

Variant names:

• chr9-126432494-A-G
• rs758970
• NM_033446.3:c.757+10546A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033446.3(MVB12B):​c.757+10546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,198 control chromosomes in the GnomAD database, including 26,004 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 0.58 (26004 hom., cov: 34)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVB12B	NM_033446.3	c.757+10546A>G		intron_variant	Intron 7 of 9	ENST00000361171.8	NP_258257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVB12B	ENST00000361171.8	c.757+10546A>G		intron_variant	Intron 7 of 9	2	NM_033446.3	ENSP00000354772.3
MVB12B	ENST00000470567.5	n.153+10546A>G		intron_variant	Intron 2 of 2	5
MVB12B	ENST00000489570.1	n.95+10546A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88405 AN: 152080 Hom.: 25963 Cov.: 34

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.581 AC: 88480 AN: 152198 Hom.: 26004 Cov.: 34 AF XY: 0.583 AC XY: 43394 AN XY: 74420

African (AFR) AF: 0.507 AC: 21054 AN: 41500

American (AMR) AF: 0.653 AC: 9992 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2056 AN: 3472

East Asian (EAS) AF: 0.690 AC: 3575 AN: 5182

South Asian (SAS) AF: 0.630 AC: 3039 AN: 4820

European-Finnish (FIN) AF: 0.593 AC: 6282 AN: 10602

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40462 AN: 68006

Other (OTH) AF: 0.588 AC: 1245 AN: 2116

Alfa AF: 0.578 Hom.: 32479

Bravo AF: 0.579

Asia WGS AF: 0.645 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.57
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: rs758970; hg19: chr9-129194773;