rs1030452

Variant names:

• chr12-21655335-T-A
• rs1030452
• NM_002300.8:c.-6-658A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-21655335-T-A
• chr12-21655335-T-C
• chr12-21655335-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002300.8(LDHB):​c.-6-658A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: LDHB NM_002300.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 2 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDHB	NM_002300.8	c.-6-658A>T		intron_variant	Intron 1 of 7	ENST00000350669.5	NP_002291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDHB	ENST00000350669.5	c.-6-658A>T		intron_variant	Intron 1 of 7	1	NM_002300.8	ENSP00000229319.1
ENSG00000285854	ENST00000647960.1	n.-6-658A>T		intron_variant	Intron 1 of 22			ENSP00000497202.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 9683

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.68
PhyloP100		0.31

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: rs1030452; hg19: chr12-21808269;