Variant 12-21638338-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002300.8(LDHB):c.713+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,298,656 control chromosomes in the GnomAD database, including 633,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.95 ( 68351 hom., cov: 30)

Exomes 𝑓: 0.99 ( 565382 hom. )

Consequence

LDHB
NM_002300.8 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

LDHB (HGNC:6541): (lactate dehydrogenase B) This gene encodes the B subunit of lactate dehydrogenase enzyme, which catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+ in a post-glycolysis process. Alternatively spliced transcript variants have been found for this gene. Recent studies have shown that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is localized in the peroxisomes. Mutations in this gene are associated with lactate dehydrogenase B deficiency. Pseudogenes have been identified on chromosomes X, 5 and 13. [provided by RefSeq, Feb 2016]

LDHB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 12-21638338-T-C is Benign according to our data. Variant chr12-21638338-T-C is described in ClinVar as [Benign]. Clinvar id is 308019.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-21638338-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDHB	NM_002300.8 linkuse as main transcript	c.713+15A>G		intron_variant		ENST00000350669.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDHB	ENST00000350669.5 linkuse as main transcript	c.713+15A>G		intron_variant		1	NM_002300.8	P1

Frequencies

GnomAD3 genomes

AF:

0.945

AC:

143474

AN:

151790

Hom.:

68309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.979

Gnomad ASJ

AF:

0.968

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.992

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.953

GnomAD3 exomes

AF:

0.983

AC:

246517

AN:

250698

Hom.:

121503

AF XY:

0.987

AC XY:

133775

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.990

Gnomad ASJ exome

AF:

0.975

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.992

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.989

GnomAD4 exome

AF:

0.993

AC:

1138178

AN:

1146748

Hom.:

565382

Cov.:

AF XY:

0.993

AC XY:

582194

AN XY:

586172

show subpopulations

Gnomad4 AFR exome

AF:

0.807

Gnomad4 AMR exome

AF:

0.989

Gnomad4 ASJ exome

AF:

0.973

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.993

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.984

GnomAD4 genome

AF:

0.945

AC:

143573

AN:

151908

Hom.:

68351

Cov.:

AF XY:

0.946

AC XY:

70225

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.815

Gnomad4 AMR

AF:

0.979

Gnomad4 ASJ

AF:

0.968

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.993

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.953

Alfa

AF:

0.969

Hom.:

13318

Bravo

AF:

0.939

Asia WGS

AF:

0.981

AC:

3411

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

DANN

Benign

0.31

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