rs4836537

Variant names:

• chr9-126402781-T-G
• rs4836537
• NM_033446.3:c.662+7084T>G

Variant summary

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

The NM_033446.3(MVB12B):​c.662+7084T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,316 control chromosomes in the GnomAD database, including 1,578 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 0.12 (1578 hom., cov: 33)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	NM_033446.3	MANE Select	c.662+7084T>G		intron	N/A	NP_258257.1	Q9H7P6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.662+7084T>G		intron	N/A	ENSP00000354772.3	Q9H7P6-1
	MVB12B	ENST00000885963.1		c.663-5639T>G		intron	N/A	ENSP00000556022.1
	MVB12B	ENST00000885962.1		c.713+7084T>G		intron	N/A	ENSP00000556021.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18911 AN: 152198 Hom.: 1575 Cov.: 33

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.124 AC: 18922 AN: 152316 Hom.: 1578 Cov.: 33 AF XY: 0.124 AC XY: 9229 AN XY: 74474

African (AFR) AF: 0.0356 AC: 1481 AN: 41584

American (AMR) AF: 0.159 AC: 2430 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 696 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1979 AN: 5182

South Asian (SAS) AF: 0.0892 AC: 431 AN: 4834

European-Finnish (FIN) AF: 0.118 AC: 1251 AN: 10608

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10114 AN: 68016

Other (OTH) AF: 0.156 AC: 329 AN: 2108

Alfa AF: 0.140 Hom.: 873

Bravo AF: 0.129

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.60
PhyloP100		0.58
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: rs4836537; hg19: chr9-129165060;