Variant rs11067231 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.*1230G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 453,606 control chromosomes in the GnomAD database, including 65,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25399 hom., cov: 30)

Exomes 𝑓: 0.50 ( 39635 hom. )

Consequence

MMAB
NM_052845.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.10

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:

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=-0.89).

BP6

Variant 12-109555798-C-A is Benign according to our data. Variant chr12-109555798-C-A is described in ClinVar as [Benign]. Clinvar id is 307039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMAB	NM_052845.4 link	c.*1230G>T		3_prime_UTR_variant	9/9	ENST00000545712.7	NP_443077.1	Q96EY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMAB	ENST00000545712 link	c.*1230G>T		3_prime_UTR_variant	9/9	1	NM_052845.4	ENSP00000445920.1		Q96EY8

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

85968

AN:

151704

Hom.:

25355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.723

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.580

GnomAD3 exomes

AF:

0.491

AC:

64022

AN:

130508

Hom.:

16399

AF XY:

0.487

AC XY:

34685

AN XY:

71230

show subpopulations

Gnomad AFR exome

AF:

0.737

Gnomad AMR exome

AF:

0.462

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.538

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.505

AC:

152368

AN:

301784

Hom.:

39635

Cov.:

AF XY:

0.498

AC XY:

85657

AN XY:

171986

show subpopulations

Gnomad4 AFR exome

AF:

0.729

Gnomad4 AMR exome

AF:

0.465

Gnomad4 ASJ exome

AF:

0.553

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.470

Gnomad4 NFE exome

AF:

0.540

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.567

AC:

86074

AN:

151822

Hom.:

25399

Cov.:

AF XY:

0.557

AC XY:

41328

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.724

Gnomad4 AMR

AF:

0.503

Gnomad4 ASJ

AF:

0.533

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.463

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.581

Alfa

AF:

0.545

Hom.:

39534

Bravo

AF:

0.580

Asia WGS

AF:

0.385

AC:

1337

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Methylmalonic aciduria, cblB type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.086

DANN

Benign

0.48

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.

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