rs11601413

chr11-18400136-C-A

Variant summary

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

The NM_005566.4(LDHA):c.244+588C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 176,080 control chromosomes in the GnomAD database, including 1,231 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 0.12 (1080 hom., cov: 32)
  • Exomes 𝑓: 0.098 (151 hom.)
• Consequence: LDHA NM_005566.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDHA	NM_005566.4	c.244+588C>A		intron_variant		ENST00000422447.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDHA	ENST00000422447.8	c.244+588C>A		intron_variant		1	NM_005566.4	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17723 AN: 152098 Hom.: 1076 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0977 AC: 2331 AN: 23864 Hom.: 151 Cov.: 0 AF XY: 0.0960 AC XY: 1196 AN XY: 12460

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0418

Gnomad4 SAS exome AF: 0.0869

Gnomad4 FIN exome AF: 0.0809

Gnomad4 NFE exome AF: 0.0978

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.117 AC: 17742 AN: 152216 Hom.: 1080 Cov.: 32 AF XY: 0.115 AC XY: 8573 AN XY: 74430

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0546

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0891

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.123

Alfa AF: 0.121 Hom.: 1090

Bravo AF: 0.120

Asia WGS AF: 0.117 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.9
Dann	Benign	0.55

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: rs11601413; hg19: chr11-18421683;