NM_021925.4:c.787-1411T>C

Variant names:

• chr2-20688505-A-G
• rs13385191
• NM_021925.4:c.787-1411T>C

Variant summary

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

The NM_021925.4(LDAH):​c.787-1411T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,202 control chromosomes in the GnomAD database, including 4,227 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 0.21 (4227 hom., cov: 31)
• Consequence: LDAH NM_021925.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350
• Publications: 98 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDAH	NM_021925.4	c.787-1411T>C		intron_variant	Intron 6 of 6	ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8	c.787-1411T>C		intron_variant	Intron 6 of 6	1	NM_021925.4	ENSP00000237822.3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31594 AN: 152084 Hom.: 4220 Cov.: 31

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.208 AC: 31599 AN: 152202 Hom.: 4227 Cov.: 31 AF XY: 0.214 AC XY: 15913 AN XY: 74386

African (AFR) AF: 0.0510 AC: 2118 AN: 41554

American (AMR) AF: 0.279 AC: 4260 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2347 AN: 5160

South Asian (SAS) AF: 0.324 AC: 1558 AN: 4808

European-Finnish (FIN) AF: 0.264 AC: 2801 AN: 10590

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16788 AN: 68014

Other (OTH) AF: 0.242 AC: 511 AN: 2108

Alfa AF: 0.240 Hom.: 18569

Bravo AF: 0.198

Asia WGS AF: 0.380 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.67
PhyloP100		0.35
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: rs13385191; hg19: chr2-20888265;