rs1677104

Variant names:

• chr12-21649500-C-T
• rs1677104
• NM_002300.8:c.130-2484G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
LDHB	NM_002300.8	c.130-2484G>A		intron_variant	Intron 2 of 7	ENST00000350669.5	NP_002291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDHB	ENST00000350669.5	c.130-2484G>A		intron_variant	Intron 2 of 7	1	NM_002300.8	ENSP00000229319.1
ENSG00000285854	ENST00000647960.1	n.130-2484G>A		intron_variant	Intron 2 of 22			ENSP00000497202.1

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

African (AFR) AF: 0.815 AC: 33850 AN: 41532

American (AMR) AF: 0.979 AC: 14979 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3362 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5179 AN: 5180

South Asian (SAS) AF: 0.993 AC: 4795 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10613 AN: 10614

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67956 AN: 68044

Other (OTH) AF: 0.954 AC: 2018 AN: 2116

Alfa AF: 0.965 Hom.: 9199

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
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs1677104; hg19: chr12-21802434;