12-21649500-C-T

Position:

• chr12-21649500-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.130-2484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 152,300 control chromosomes in the GnomAD database, including 68,533 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 0.95 (68533 hom., cov: 33)
• Consequence: LDHB NM_002300.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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	Protein	UniProt
LDHB	NM_002300.8	c.130-2484G>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.130-2484G>A		intron_variant		1	NM_002300.8	ENSP00000229319	P1

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143855 AN: 152182 Hom.: 68491 Cov.: 33

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: 0.954

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

GnomAD4 genome AF: 0.945 AC: 143954 AN: 152300 Hom.: 68533 Cov.: 33 AF XY: 0.946 AC XY: 70461 AN XY: 74490

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: 0.954

Alfa AF: 0.969 Hom.: 8911

Bravo AF: 0.938

Asia WGS AF: 0.981 AC: 3411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.23

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: rs1677104; hg19: chr12-21802434;