rs10987251

Positions:

• chr9-126340715-G-A

Variant summary

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

The NM_033446.3(MVB12B):​c.204+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,481,558 control chromosomes in the GnomAD database, including 72,478 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 0.30 (6912 hom., cov: 32)
  • Exomes 𝑓: 0.31 (65566 hom.)
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVB12B	NM_033446.3	c.204+85G>A		intron_variant		ENST00000361171.8	NP_258257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVB12B	ENST00000361171.8	c.204+85G>A		intron_variant		2	NM_033446.3	ENSP00000354772	P1
MVB12B	ENST00000489637.3	c.204+85G>A		intron_variant		1		ENSP00000485994
MVB12B	ENST00000402437.2	c.159+85G>A		intron_variant		3		ENSP00000384751

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45572 AN: 151968 Hom.: 6912 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.313 AC: 416333 AN: 1329472 Hom.: 65566 AF XY: 0.312 AC XY: 205251 AN XY: 658878

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.300 AC: 45588 AN: 152086 Hom.: 6912 Cov.: 32 AF XY: 0.302 AC XY: 22485 AN XY: 74338

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.280

Alfa AF: 0.314 Hom.: 3611

Bravo AF: 0.292

Asia WGS AF: 0.295 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10987251; hg19: chr9-129102994; COSMIC: COSV63257363;