dbSNP rs2046325: LDAH:c.703+25A>G (chr2-20739946-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021925.4(LDAH):c.703+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,528,078 control chromosomes in the GnomAD database, including 75,023 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 0.25 ( 6026 hom., cov: 33)

Exomes 𝑓: 0.31 ( 68997 hom. )

Consequence

LDAH
NM_021925.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.192

Publications

5 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDAH	NM_021925.4 link	c.703+25A>G		intron_variant	Intron 5 of 6	ENST00000237822.8	NP_068744.1	Q9H6V9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8 link	c.703+25A>G		intron_variant	Intron 5 of 6	1	NM_021925.4	ENSP00000237822.3		Q9H6V9-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38215

AN:

151924

Hom.:

6019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0641

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.291

GnomAD2 exomes

AF:

0.327

AC:

80777

AN:

246952

AF XY:

0.338

show subpopulations

Gnomad AFR exome

AF:

0.0548

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.442

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.307

AC:

422329

AN:

1376036

Hom.:

68997

Cov.:

AF XY:

0.313

AC XY:

215385

AN XY:

688902

show subpopulations

African (AFR)

AF:

0.0575

AC:

1822

AN:

31666

American (AMR)

AF:

0.342

AC:

15136

AN:

44310

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

9606

AN:

25516

East Asian (EAS)

AF:

0.508

AC:

19923

AN:

39228

South Asian (SAS)

AF:

0.461

AC:

38835

AN:

84192

European-Finnish (FIN)

AF:

0.299

AC:

15690

AN:

52552

Middle Eastern (MID)

AF:

0.422

AC:

2359

AN:

5596

European-Non Finnish (NFE)

AF:

0.291

AC:

300818

AN:

1035342

Other (OTH)

AF:

0.315

AC:

18140

AN:

57634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

14548

29096

43645

58193

72741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9694

19388

29082

38776

48470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.251

AC:

38215

AN:

152042

Hom.:

6026

Cov.:

AF XY:

0.259

AC XY:

19242

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0639

AC:

2654

AN:

41558

American (AMR)

AF:

0.341

AC:

5204

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1315

AN:

3468

East Asian (EAS)

AF:

0.477

AC:

2457

AN:

5154

South Asian (SAS)

AF:

0.461

AC:

2224

AN:

4828

European-Finnish (FIN)

AF:

0.299

AC:

3144

AN:

10512

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20239

AN:

67944

Other (OTH)

AF:

0.300

AC:

632

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1382

2764

4146

5528

6910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.279

Hom.:

2789

Bravo

AF:

0.240

Asia WGS

AF:

0.462

AC:

1607

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.84

(source)

DANN

Benign

0.85

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over