12-21650836-C-T

Position:

• chr12-21650836-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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]

ENSG00000285854 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHB	NM_002300.8	c.129+3707G>A		intron_variant		ENST00000350669.5	NP_002291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDHB	ENST00000350669.5	c.129+3707G>A		intron_variant		1	NM_002300.8	ENSP00000229319.1
ENSG00000285854	ENST00000647960.1	n.129+3707G>A		intron_variant				ENSP00000497202.1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 107001 AN: 151956 Hom.: 38109 Cov.: 33

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.: 33 AF XY: 0.700 AC XY: 52013 AN XY: 74342

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.720

Alfa AF: 0.718 Hom.: 18035

Bravo AF: 0.719

Asia WGS AF: 0.755 AC: 2623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs1650307; hg19: chr12-21803770;