9-126339110-C-G

Variant names:

• chr9-126339110-C-G
• rs531599
• NM_033446.3:c.82-1398C>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.82-1398C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,216 control chromosomes in the GnomAD database, including 2,805 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 0.19 (2805 hom., cov: 33)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	NM_033446.3	MANE Select	c.82-1398C>G		intron	N/A	NP_258257.1
	MVB12B	NM_001011703.3		c.82-1398C>G		intron	N/A	NP_001011703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.82-1398C>G		intron	N/A	ENSP00000354772.3
	MVB12B	ENST00000489637.3	TSL:1	c.82-1398C>G		intron	N/A	ENSP00000485994.1
	MVB12B	ENST00000885963.1		c.82-1398C>G		intron	N/A	ENSP00000556022.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28639 AN: 152096 Hom.: 2794 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.188 AC: 28675 AN: 152216 Hom.: 2805 Cov.: 33 AF XY: 0.183 AC XY: 13642 AN XY: 74418

African (AFR) AF: 0.165 AC: 6870 AN: 41524

American (AMR) AF: 0.190 AC: 2912 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3470

East Asian (EAS) AF: 0.177 AC: 916 AN: 5168

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1074 AN: 10606

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14404 AN: 68010

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.0868 Hom.: 117

Bravo AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0020
DANN	Benign	0.55
PhyloP100		-2.5
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: rs531599; hg19: chr9-129101389;