chr2-20747437-T-C

Variant names:

• chr2-20747437-T-C
• rs667529
• NM_021925.4:c.469-7232A>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.469-7232A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,918 control chromosomes in the GnomAD database, including 12,730 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 0.40 (12730 hom., cov: 32)
• Consequence: LDAH NM_021925.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDAH	NM_021925.4	c.469-7232A>G		intron_variant	Intron 4 of 6	ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8	c.469-7232A>G		intron_variant	Intron 4 of 6	1	NM_021925.4	ENSP00000237822.3

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60438 AN: 151798 Hom.: 12721 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.398 AC: 60474 AN: 151918 Hom.: 12730 Cov.: 32 AF XY: 0.403 AC XY: 29905 AN XY: 74240

African (AFR) AF: 0.272 AC: 11254 AN: 41446

American (AMR) AF: 0.477 AC: 7267 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1965 AN: 3470

East Asian (EAS) AF: 0.504 AC: 2598 AN: 5152

South Asian (SAS) AF: 0.648 AC: 3123 AN: 4820

European-Finnish (FIN) AF: 0.369 AC: 3898 AN: 10556

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28910 AN: 67916

Other (OTH) AF: 0.465 AC: 982 AN: 2114

Alfa AF: 0.427 Hom.: 51779

Bravo AF: 0.395

Asia WGS AF: 0.579 AC: 2010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.59
PhyloP100		-0.42
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: rs667529; hg19: chr2-20947197;