rs2286885

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033446.3(MVB12B):​c.873+176A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,144 control chromosomes in the GnomAD database, including 13,057 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 ( 13057 hom., cov: 33)

Consequence

MVB12B
NM_033446.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.390
Variant links:
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]

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ACMG classification

Classification made for transcript

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 = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MVB12BNM_033446.3 linkuse as main transcriptc.873+176A>C intron_variant ENST00000361171.8
MVB12BXM_005252297.1 linkuse as main transcriptc.828+176A>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MVB12BENST00000361171.8 linkuse as main transcriptc.873+176A>C intron_variant 2 NM_033446.3 P1Q9H7P6-1
MVB12BENST00000485886.1 linkuse as main transcriptn.672+176A>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.401
AC:
60941
AN:
152026
Hom.:
13048
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.254
Gnomad AMI
AF:
0.402
Gnomad AMR
AF:
0.432
Gnomad ASJ
AF:
0.488
Gnomad EAS
AF:
0.707
Gnomad SAS
AF:
0.396
Gnomad FIN
AF:
0.456
Gnomad MID
AF:
0.411
Gnomad NFE
AF:
0.446
Gnomad OTH
AF:
0.440
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.401
AC:
60969
AN:
152144
Hom.:
13057
Cov.:
33
AF XY:
0.401
AC XY:
29848
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.255
Gnomad4 AMR
AF:
0.431
Gnomad4 ASJ
AF:
0.488
Gnomad4 EAS
AF:
0.708
Gnomad4 SAS
AF:
0.395
Gnomad4 FIN
AF:
0.456
Gnomad4 NFE
AF:
0.446
Gnomad4 OTH
AF:
0.438
Alfa
AF:
0.435
Hom.:
6835
Bravo
AF:
0.403
Asia WGS
AF:
0.546
AC:
1898
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
7.2
DANN
Benign
0.37

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2286885; hg19: chr9-129246487; API