11-18394766-A-C

Position:

• chr11-18394766-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005566.4(LDHA):​c.-25+130A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 428,438 control chromosomes in the GnomAD database, including 929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (766 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (163 hom.)
• Consequence: LDHA NM_005566.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-18394766-A-C is Benign according to our data. Variant chr11-18394766-A-C is described in ClinVar as [Benign]. Clinvar id is 1292604.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHA	NM_005566.4	c.-25+130A>C		intron_variant		ENST00000422447.8	NP_005557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDHA	ENST00000422447.8	c.-25+130A>C		intron_variant		1	NM_005566.4	ENSP00000395337	P1

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8476 AN: 152112 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.0497

GnomAD4 exome AF: 0.00883 AC: 2439 AN: 276208 Hom.: 163 Cov.: 0 AF XY: 0.00693 AC XY: 1080 AN XY: 155888

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0135

Gnomad4 EAS exome AF: 0.000113

Gnomad4 SAS exome AF: 0.000565

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.0160

GnomAD4 genome AF: 0.0558 AC: 8499 AN: 152230 Hom.: 766 Cov.: 32 AF XY: 0.0535 AC XY: 3983 AN XY: 74432

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.0252

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0350 Hom.: 59

Bravo AF: 0.0644

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12278153; hg19: chr11-18416313;