11-18397138-A-G

Position:

• chr11-18397138-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.494

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 -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/exons	MANE	Protein	UniProt
LDHA	NM_005566.4	c.126+170A>G		intron_variant		ENST00000422447.8	NP_005557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDHA	ENST00000422447.8	c.126+170A>G		intron_variant		1	NM_005566.4	ENSP00000395337	P1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2741 AN: 152242 Hom.: 38 Cov.: 33

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.: 6 AF XY: 0.0261 AC XY: 6116 AN XY: 234456

Gnomad4 AFR exome AF: 0.00378

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.0128

Gnomad4 EAS exome AF: 0.0000314

Gnomad4 SAS exome AF: 0.0653

Gnomad4 FIN exome AF: 0.0329

Gnomad4 NFE exome AF: 0.0207

Gnomad4 OTH exome AF: 0.0204

GnomAD4 genome AF: 0.0180 AC: 2743 AN: 152360 Hom.: 39 Cov.: 33 AF XY: 0.0188 AC XY: 1400 AN XY: 74506

Gnomad4 AFR AF: 0.00440

Gnomad4 AMR AF: 0.0259

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0233 Hom.: 8

Bravo AF: 0.0164

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.73

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: rs149686758; hg19: chr11-18418685;