rs2896526

chr11-18398259-A-Gchr11-18398259-A-T

Variant summary

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

The NM_005566.4(LDHA):c.127-1172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,110 control chromosomes in the GnomAD database, including 1,723 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 0.15 (1723 hom., cov: 33)
• Consequence: LDHA NM_005566.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

Genes affected

LDHA (HGNC:6535): (lactate dehydrogenase A) This gene encodes the A subunit of lactate dehydrogenase enzyme which catalyzes the reversible conversion of pyruvate to lactate with the concomitant oxidation of NADH to NAD in anaerobic glycolysis. The protein is found predominantly in skeletal muscle and belongs to the lactate dehydrogenase family. Mutations in this gene have been linked to exertional myoglobinuria. The human genome contains several non-transcribed pseudogenes of this gene. [provided by RefSeq, Sep 2023]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDHA	NM_005566.4	c.127-1172A>G		intron_variant		ENST00000422447.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDHA	ENST00000422447.8	c.127-1172A>G		intron_variant		1	NM_005566.4	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22138 AN: 151992 Hom.: 1722 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.146 AC: 22140 AN: 152110 Hom.: 1723 Cov.: 33 AF XY: 0.143 AC XY: 10634 AN XY: 74356

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0656

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.163

Alfa AF: 0.165 Hom.: 3197

Bravo AF: 0.150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.34
Dann	Benign	0.89

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: rs2896526; hg19: chr11-18419806;