rs116817482

Variant names:

• chr11-18396211-G-T
• rs116817482
• NM_005566.4:c.-24-608G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005566.4(LDHA):​c.-24-608G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 266,348 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00049 (0 hom.)
• Consequence: LDHA NM_005566.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.872
• Publications: 0 publications found

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]

LDHA Gene-Disease associations (from GenCC):

• glycogen storage disease due to lactate dehydrogenase M-subunit deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ENSG00000302300 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-18396211-G-T is Benign according to our data. Variant chr11-18396211-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1181635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00325 (495/152382) while in subpopulation AFR AF = 0.0114 (475/41596). AF 95% confidence interval is 0.0106. There are 6 homozygotes in GnomAd4. There are 241 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005566.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDHA	NM_005566.4	MANE Select	c.-24-608G>T		intron	N/A	NP_005557.1	P00338-1
	LDHA	NM_001135239.2		c.-24-608G>T		intron	N/A	NP_001128711.1	P00338-4
	LDHA	NM_001165415.2		c.-24-608G>T		intron	N/A	NP_001158887.1	P00338-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDHA	ENST00000422447.8	TSL:1 MANE Select	c.-24-608G>T		intron	N/A	ENSP00000395337.3	P00338-1
	LDHA	ENST00000545215.5	TSL:1	n.-24-608G>T		intron	N/A	ENSP00000442637.1	F5GWW2
	LDHA	ENST00000859177.1		c.-155-269G>T		intron	N/A	ENSP00000529236.1

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 494 AN: 152264 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000491 AC: 56 AN: 113966 Hom.: 0 AF XY: 0.000494 AC XY: 28 AN XY: 56720

African (AFR) AF: 0.0102 AC: 42 AN: 4124

American (AMR) AF: 0.000317 AC: 1 AN: 3156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5046

East Asian (EAS) AF: 0.00 AC: 0 AN: 10412

South Asian (SAS) AF: 0.00 AC: 0 AN: 1104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 654

European-Non Finnish (NFE) AF: 0.0000269 AC: 2 AN: 74446

Other (OTH) AF: 0.00135 AC: 11 AN: 8138

GnomAD4 genome AF: 0.00325 AC: 495 AN: 152382 Hom.: 6 Cov.: 33 AF XY: 0.00323 AC XY: 241 AN XY: 74522

African (AFR) AF: 0.0114 AC: 475 AN: 41596

American (AMR) AF: 0.000849 AC: 13 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00180 Hom.: 1

Bravo AF: 0.00356

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		-0.87
PromoterAI		0.0032	Neutral

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: rs116817482; hg19: chr11-18417758;