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. Variant has been reported in ClinVar as (no stars).

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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021925.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LDAH	NM_021925.4	MANE Select	c.703+25A>G	intron	N/A	NP_068744.1	Q9H6V9-1
LDAH	NM_001282719.2		c.577+25A>G	intron	N/A	NP_001269648.1	A0A0A0MSH6
LDAH	NM_001282720.2		c.559+25A>G	intron	N/A	NP_001269649.1	Q9H6V9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LDAH	ENST00000237822.8	TSL:1 MANE Select	c.703+25A>G	intron	N/A	ENSP00000237822.3	Q9H6V9-1
LDAH	ENST00000911673.1		c.703+25A>G	intron	N/A	ENSP00000581732.1
LDAH	ENST00000381090.7	TSL:5	c.703+25A>G	intron	N/A	ENSP00000370480.3	B5MDU6

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over