rs4837082

Variant names:

• chr9-126425544-G-A
• rs4837082
• NM_033446.3:c.757+3596G>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+3596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,206 control chromosomes in the GnomAD database, including 1,769 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 0.13 (1769 hom., cov: 33)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 2 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 = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVB12B	NM_033446.3	c.757+3596G>A		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+3596G>A		intron_variant	Intron 7 of 9	2	NM_033446.3	ENSP00000354772.3
MVB12B	ENST00000470567.5	n.153+3596G>A		intron_variant	Intron 2 of 2	5
MVB12B	ENST00000489570.1	n.95+3596G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20488 AN: 152088 Hom.: 1765 Cov.: 33

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.135 AC: 20509 AN: 152206 Hom.: 1769 Cov.: 33 AF XY: 0.134 AC XY: 9969 AN XY: 74424

African (AFR) AF: 0.0547 AC: 2271 AN: 41528

American (AMR) AF: 0.189 AC: 2892 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2062 AN: 5178

South Asian (SAS) AF: 0.0915 AC: 441 AN: 4822

European-Finnish (FIN) AF: 0.117 AC: 1235 AN: 10590

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10345 AN: 68012

Other (OTH) AF: 0.170 AC: 360 AN: 2112

Alfa AF: 0.156 Hom.: 882

Bravo AF: 0.143

Asia WGS AF: 0.235 AC: 817 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	0.034
DANN	Benign	0.56
PhyloP100		-2.2
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: rs4837082; hg19: chr9-129187823;