rs4837082

Positions:

• chr9-126425544-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• 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/exons	MANE	Protein	UniProt
MVB12B	NM_033446.3	c.757+3596G>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+3596G>A		intron_variant		2	NM_033446.3	ENSP00000354772	P1
MVB12B	ENST00000470567.5	n.153+3596G>A		intron_variant, non_coding_transcript_variant		5
MVB12B	ENST00000489570.1	n.95+3596G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.0915

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.170

Alfa AF: 0.146 Hom.: 410

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4837082; hg19: chr9-129187823;