rs340623

Positions:

• chr2-20732518-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021925.4(LDAH):​c.703+7453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,096 control chromosomes in the GnomAD database, including 11,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11040 hom., cov: 32)
• Consequence: LDAH NM_021925.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

Genes affected

LDAH (HGNC:26145): (lipid droplet associated hydrolase) Predicted to enable lipase activity. Predicted to be involved in lipid storage. Predicted to be located in endoplasmic reticulum. Predicted to be active in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

LDAH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDAH	NM_021925.4	c.703+7453A>G		intron_variant		ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8	c.703+7453A>G		intron_variant		1	NM_021925.4	ENSP00000237822.3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54044 AN: 151978 Hom.: 11033 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.355 AC: 54049 AN: 152096 Hom.: 11040 Cov.: 32 AF XY: 0.362 AC XY: 26891 AN XY: 74370

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.425

Alfa AF: 0.363 Hom.: 1373

Bravo AF: 0.348

Asia WGS AF: 0.547 AC: 1899 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.71

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: rs340623; hg19: chr2-20932278;