rs1012354

Variant names:

• chr12-21712280-C-A
• rs1012354
• ENST00000539782.1:c.-7+25417G>T

Variant summary

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

The ENST00000539782.1(LDHB):​c.-7+25417G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,066 control chromosomes in the GnomAD database, including 478 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 0.043 (478 hom., cov: 32)
• Consequence: LDHB ENST00000539782.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731

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]

ENSG00000256615 (HGNC:58193):

LOC105369689 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369689	XR_007063241.1	n.460-47634C>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDHB	ENST00000539782.1	c.-7+25417G>T		intron_variant	Intron 2 of 4	3		ENSP00000442680.1
LDHB	ENST00000535112.1	n.146+25417G>T		intron_variant	Intron 2 of 3	5
ENSG00000256615	ENST00000541860.1	n.460-47634C>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6490 AN: 151948 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000677

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0428 AC: 6511 AN: 152066 Hom.: 478 Cov.: 32 AF XY: 0.0417 AC XY: 3102 AN XY: 74350

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.000677

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0248 Hom.: 33

Bravo AF: 0.0484

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1012354; hg19: chr12-21865214;