Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM1BS2

The NM_002300.8(LDHB):c.19A>G(p.Lys7Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

LDHB
NM_002300.8 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 3.17

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

glycogen storage disease due to lactate dehydrogenase H-subunit deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LDHB links:

ENSG00000285854 (HGNC:):

ENSG00000285854 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM1

In a modified_residue N6-acetyllysine (size 0) in uniprot entity LDHB_HUMAN

BS2

High AC in GnomAdExome4 at 65 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002300.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LDHB	NM_002300.8	MANE Select	c.19A>G	p.Lys7Glu	missense	Exon 2 of 8	NP_002291.1
LDHB	NM_001315537.2		c.19A>G	p.Lys7Glu	missense	Exon 2 of 8	NP_001302466.1
LDHB	NM_001174097.3		c.19A>G	p.Lys7Glu	missense	Exon 2 of 8	NP_001167568.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LDHB	ENST00000350669.5	TSL:1 MANE Select	c.19A>G	p.Lys7Glu	missense	Exon 2 of 8	ENSP00000229319.1
ENSG00000285854	ENST00000647960.1		n.19A>G		non_coding_transcript_exon	Exon 2 of 23	ENSP00000497202.1
LDHB	ENST00000673047.2		c.19A>G	p.Lys7Glu	missense	Exon 2 of 8	ENSP00000500484.2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251478

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000531

AC:

AN:

1111856

Other (OTH)

AF:

0.0000994

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000620

Hom.:

Bravo

AF:

0.0000340

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Affects

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

(source)

DANN

Benign

0.92

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.74

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.44

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

1.5

PhyloP100

3.2

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.73

REVEL

Uncertain

0.59

Sift

Benign

0.24

Sift4G

Benign

0.31

Polyphen

0.33

Vest4

0.82

MVP

0.95

MPC

0.56

ClinPred

0.15

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.56

gMVP

0.51

Mutation Taster

=6/94

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs118203897

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over