dbSNP rs1650307: LDHB:c.129+3707G>A (chr12-21650836-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002300.8(LDHB):c.129+3707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,076 control chromosomes in the GnomAD database, including 38,134 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 0.70 ( 38134 hom., cov: 33)

Consequence

LDHB
NM_002300.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0670

Publications

3 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: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
LDHB	NM_002300.8	MANE Select	c.129+3707G>A	intron	N/A	NP_002291.1	Q5U077
LDHB	NM_001315537.2		c.129+3707G>A	intron	N/A	NP_001302466.1	A0A5F9ZHM4
LDHB	NM_001174097.3		c.129+3707G>A	intron	N/A	NP_001167568.1	Q5U077

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LDHB	ENST00000350669.5	TSL:1 MANE Select	c.129+3707G>A	intron	N/A	ENSP00000229319.1	P07195
ENSG00000285854	ENST00000647960.1		n.129+3707G>A	intron	N/A	ENSP00000497202.1	A0A3B3IS95
LDHB	ENST00000673047.2		c.129+3707G>A	intron	N/A	ENSP00000500484.2	A0A5F9ZHM4

Frequencies

GnomAD3 genomes

AF:

0.704

AC:

107001

AN:

151956

Hom.:

38109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.840

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.871

Gnomad SAS

AF:

0.657

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.722

Gnomad OTH

AF:

0.721

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.704

AC:

107070

AN:

152076

Hom.:

38134

Cov.:

AF XY:

0.700

AC XY:

52013

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.647

AC:

26798

AN:

41446

American (AMR)

AF:

0.786

AC:

12015

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.753

AC:

2616

AN:

3472

East Asian (EAS)

AF:

0.871

AC:

4507

AN:

5176

South Asian (SAS)

AF:

0.658

AC:

3170

AN:

4818

European-Finnish (FIN)

AF:

0.606

AC:

6404

AN:

10570

Middle Eastern (MID)

AF:

0.690

AC:

203

AN:

294

European-Non Finnish (NFE)

AF:

0.722

AC:

49070

AN:

67986

Other (OTH)

AF:

0.720

AC:

1521

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1640

3280

4920

6560

8200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.718

Hom.:

20210

Bravo

AF:

0.719

Asia WGS

AF:

0.755

AC:

2623

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.3

(source)

DANN

Benign

0.54

PhyloP100

-0.067

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over