rs4971516

Variant names:

• chr2-20703255-T-C
• rs4971516
• NM_021925.4:c.704-1603A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021925.4(LDAH):​c.704-1603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 152,328 control chromosomes in the GnomAD database, including 474 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 0.067 (474 hom., cov: 33)
• Consequence: LDAH NM_021925.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 16 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDAH	NM_021925.4	c.704-1603A>G		intron_variant	Intron 5 of 6	ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8	c.704-1603A>G		intron_variant	Intron 5 of 6	1	NM_021925.4	ENSP00000237822.3

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10170 AN: 152210 Hom.: 472 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0626

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

GnomAD4 genome AF: 0.0669 AC: 10194 AN: 152328 Hom.: 474 Cov.: 33 AF XY: 0.0690 AC XY: 5137 AN XY: 74482

African (AFR) AF: 0.101 AC: 4209 AN: 41568

American (AMR) AF: 0.0450 AC: 689 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.134 AC: 696 AN: 5188

South Asian (SAS) AF: 0.112 AC: 539 AN: 4830

European-Finnish (FIN) AF: 0.104 AC: 1103 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0395 AC: 2684 AN: 68034

Other (OTH) AF: 0.0619 AC: 131 AN: 2116

Alfa AF: 0.0488 Hom.: 737

Bravo AF: 0.0651

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		-0.054
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

Other links and lift over

dbSNP: rs4971516; hg19: chr2-20903015;