9-126487346-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033446.3(MVB12B):c.873+3314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,944 control chromosomes in the GnomAD database, including 12,779 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 0.40 (12779 hom., cov: 32)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MVB12B	NM_033446.3	c.873+3314C>T		intron_variant		ENST00000361171.8
MVB12B	XM_005252297.1	c.828+3314C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MVB12B	ENST00000361171.8	c.873+3314C>T		intron_variant		2	NM_033446.3	P1
MVB12B	ENST00000485886.1	n.672+3314C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60090 AN: 151824 Hom.: 12771 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.396 AC: 60117 AN: 151944 Hom.: 12779 Cov.: 32 AF XY: 0.396 AC XY: 29408 AN XY: 74264

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.430

Alfa AF: 0.280 Hom.: 716

Bravo AF: 0.397

Asia WGS AF: 0.541 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0090
Dann	Benign	0.62

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: rs10819169; hg19: chr9-129249625;