Genetic Variant LDHA:c.126+170A>G (chr11-18397138-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005566.4(LDHA):c.126+170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 597,000 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 39 hom., cov: 33)

Exomes 𝑓: 0.024 ( 245 hom. )

Consequence

LDHA
NM_005566.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.494

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-18397138-A-G is Benign according to our data. Variant chr11-18397138-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1216145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDHA	NM_005566.4 link	c.126+170A>G		intron_variant	Intron 2 of 7	ENST00000422447.8	NP_005557.1	P00338-1V9HWB9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDHA	ENST00000422447.8 link	c.126+170A>G		intron_variant	Intron 2 of 7	1	NM_005566.4	ENSP00000395337.3		P00338-1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2741

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00441

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0256

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0608

Gnomad FIN

AF:

0.0353

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.0243

AC:

10785

AN:

444640

Hom.:

245

Cov.:

AF XY:

0.0261

AC XY:

6116

AN XY:

234456

show subpopulations

Gnomad4 AFR exome

AF:

0.00378

AC:

AN:

12980

Gnomad4 AMR exome

AF:

0.0476

AC:

791

AN:

16630

Gnomad4 ASJ exome

AF:

0.0128

AC:

167

AN:

13010

Gnomad4 EAS exome

AF:

0.0000314

AC:

AN:

31806

Gnomad4 SAS exome

AF:

0.0653

AC:

2469

AN:

37812

Gnomad4 FIN exome

AF:

0.0329

AC:

1140

AN:

34638

Gnomad4 NFE exome

AF:

0.0207

AC:

5588

AN:

269314

Gnomad4 Remaining exome

AF:

0.0204

AC:

509

AN:

24944

Heterozygous variant carriers

494

988

1483

1977

2471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0180

AC:

2743

AN:

152360

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

1400

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00440

AC:

0.0044001

AN:

0.0044001

Gnomad4 AMR

AF:

0.0259

AC:

0.0258722

AN:

0.0258722

Gnomad4 ASJ

AF:

0.0104

AC:

0.0103687

AN:

0.0103687

Gnomad4 EAS

AF:

0.000963

AC:

0.00096302

AN:

0.00096302

Gnomad4 SAS

AF:

0.0615

AC:

0.0614652

AN:

0.0614652

Gnomad4 FIN

AF:

0.0353

AC:

0.0353374

AN:

0.0353374

Gnomad4 NFE

AF:

0.0205

AC:

0.0205479

AN:

0.0205479

Gnomad4 OTH

AF:

0.0147

AC:

0.0146641

AN:

0.0146641

Heterozygous variant carriers

142

284

427

569

711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0233

Hom.:

Bravo

AF:

0.0164

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 22, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over