rs184316811

Variant names:

• chr9-126395571-A-G
• rs184316811
• NM_033446.3:c.540-4A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_033446.3(MVB12B):​c.540-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,613,420 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (2 hom.)
• Consequence: MVB12B NM_033446.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002417
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.619
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-126395571-A-G is Benign according to our data. Variant chr9-126395571-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3052638.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.540-4A>G		splice_region intron	N/A	NP_258257.1	Q9H7P6-1
	MVB12B	NM_001011703.3		c.540-4A>G		splice_region intron	N/A	NP_001011703.1	Q9H7P6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.540-4A>G		splice_region intron	N/A	ENSP00000354772.3	Q9H7P6-1
	MVB12B	ENST00000489637.3	TSL:1	c.540-4A>G		splice_region intron	N/A	ENSP00000485994.1	Q9H7P6-2
	MVB12B	ENST00000885963.1		c.540-4A>G		splice_region intron	N/A	ENSP00000556022.1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00237

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00139 AC: 348 AN: 250632 AF XY: 0.00144

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00231

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.00213 AC: 3108 AN: 1461148 Hom.: 2 Cov.: 30 AF XY: 0.00208 AC XY: 1509 AN XY: 726866

African (AFR) AF: 0.000329 AC: 11 AN: 33412

American (AMR) AF: 0.00234 AC: 104 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86092

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00261 AC: 2905 AN: 1111798

Other (OTH) AF: 0.00134 AC: 81 AN: 60352

GnomAD4 genome AF: 0.00143 AC: 218 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.00124 AC XY: 92 AN XY: 74452

African (AFR) AF: 0.000385 AC: 16 AN: 41552

American (AMR) AF: 0.00235 AC: 36 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00238 AC: 162 AN: 67992

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.00165

EpiCase AF: 0.00333

EpiControl AF: 0.00362

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MVB12B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.76
PhyloP100		0.62
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.18		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: rs184316811; hg19: chr9-129157850;