rs118203895

Variant names:

• chr12-21642032-C-T
• rs118203895
• NM_002300.8:c.515G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-21642032-C-T
• chr12-21642032-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_002300.8(LDHB):​c.515G>A​(p.Arg172His) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: LDHB NM_002300.8 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 5.04
• Publications: 8 publications found

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

ENSG00000285854 (HGNC:):

ACMG classification

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

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899
• BS2: High AC in GnomAdExome4 at 14 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDHB	NM_002300.8	MANE Select	c.515G>A	p.Arg172His	missense	Exon 5 of 8	NP_002291.1	Q5U077
	LDHB	NM_001315537.2		c.515G>A	p.Arg172His	missense	Exon 5 of 8	NP_001302466.1	A0A5F9ZHM4
	LDHB	NM_001174097.3		c.515G>A	p.Arg172His	missense	Exon 5 of 8	NP_001167568.1	Q5U077

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDHB	ENST00000350669.5	TSL:1 MANE Select	c.515G>A	p.Arg172His	missense	Exon 5 of 8	ENSP00000229319.1	P07195
	ENSG00000285854	ENST00000647960.1		n.515G>A		non_coding_transcript_exon	Exon 5 of 23	ENSP00000497202.1	A0A3B3IS95
	LDHB	ENST00000673047.2		c.515G>A	p.Arg172His	missense	Exon 5 of 8	ENSP00000500484.2	A0A5F9ZHM4

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151798 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461382 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726980

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111640

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151798 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74138

African (AFR) AF: 0.00 AC: 0 AN: 41312

American (AMR) AF: 0.00 AC: 0 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Affects

Revision: no assertion criteria provided

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	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		5.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.056	T
Polyphen		0.34	B
Vest4		0.62
MutPred		0.81		Gain of catalytic residue at S168 (P = 0)
MVP		0.86
MPC		0.36
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.77
Mutation Taster		=4/96	disease causing

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

Other links and lift over

dbSNP: rs118203895; hg19: chr12-21794966;