11-18396036-G-A

Position:

• chr11-18396036-G-A

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.-24-783G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,274 control chromosomes in the GnomAD database, including 896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (896 hom., cov: 33)
• Consequence: LDHA NM_005566.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.817

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-18396036-G-A is Benign according to our data. Variant chr11-18396036-G-A is described in ClinVar as [Benign]. Clinvar id is 1253811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHA	NM_005566.4	c.-24-783G>A		intron_variant		ENST00000422447.8	NP_005557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDHA	ENST00000422447.8	c.-24-783G>A		intron_variant		1	NM_005566.4	ENSP00000395337.3

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15497 AN: 152156 Hom.: 893 Cov.: 33

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0550

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15507 AN: 152274 Hom.: 896 Cov.: 33 AF XY: 0.101 AC XY: 7521 AN XY: 74464

Gnomad4 AFR AF: 0.0614

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0893

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.112

Alfa AF: 0.105 Hom.: 105

Bravo AF: 0.103

Asia WGS AF: 0.113 AC: 391 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 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.95
DANN	Benign	0.78

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: rs4757651; hg19: chr11-18417583;