9-126487346-C-T

Variant names:

• chr9-126487346-C-T
• rs10819169
• NM_033446.3:c.873+3314C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 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.873+3314C>T		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.873+3314C>T		intron	N/A	ENSP00000354772.3	Q9H7P6-1
	MVB12B	ENST00000885963.1		c.1008+3314C>T		intron	N/A	ENSP00000556022.1
	MVB12B	ENST00000885962.1		c.924+3314C>T		intron	N/A	ENSP00000556021.1

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

African (AFR) AF: 0.241 AC: 10011 AN: 41462

American (AMR) AF: 0.428 AC: 6541 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3472

East Asian (EAS) AF: 0.702 AC: 3611 AN: 5142

South Asian (SAS) AF: 0.392 AC: 1889 AN: 4818

European-Finnish (FIN) AF: 0.455 AC: 4791 AN: 10528

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30197 AN: 67926

Other (OTH) AF: 0.430 AC: 908 AN: 2110

Alfa AF: 0.278 Hom.: 742

Bravo AF: 0.397

Asia WGS AF: 0.541 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.62
PhyloP100		-2.8
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: rs10819169; hg19: chr9-129249625;