Variant rs2287180 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052845.4(MMAB):c.519+157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,583,266 control chromosomes in the GnomAD database, including 23,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2258 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21717 hom. )

Consequence

MMAB
NM_052845.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.288

Variant links:

Genes affected

MMAB (HGNC:19331): (metabolism of cobalamin associated B) This gene encodes a protein that catalyzes the final step in the conversion of vitamin B(12) into adenosylcobalamin (AdoCbl), a vitamin B12-containing coenzyme for methylmalonyl-CoA mutase. Mutations in the gene are the cause of vitamin B12-dependent methylmalonic aciduria linked to the cblB complementation group. Alternatively spliced transcript variants have been found. [provided by RefSeq, Apr 2011]

MMAB links:

MMAB (HGNC:):

MMAB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-109561263-G-A is Benign according to our data. Variant chr12-109561263-G-A is described in ClinVar as [Benign]. Clinvar id is 680637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMAB	NM_052845.4 linkuse as main transcript	c.519+157C>T		intron_variant		ENST00000545712.7	NP_443077.1	Q96EY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMAB	ENST00000545712.7 linkuse as main transcript	c.519+157C>T		intron_variant		1	NM_052845.4	ENSP00000445920.1		Q96EY8

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25731

AN:

152032

Hom.:

2262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0989

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.165

AC:

34166

AN:

207258

Hom.:

2788

AF XY:

0.164

AC XY:

18821

AN XY:

114444

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.173

AC:

247096

AN:

1431116

Hom.:

21717

Cov.:

AF XY:

0.171

AC XY:

121581

AN XY:

711236

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.169

AC:

25738

AN:

152150

Hom.:

2258

Cov.:

AF XY:

0.163

AC XY:

12161

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0989

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.176

Hom.:

435

Bravo

AF:

0.176

Asia WGS

AF:

0.150

AC:

523

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.8

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over