dbSNP rs4823173: PNPLA3:c.487-28G>A (chr22-43932850-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_025225.3(PNPLA3):c.487-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,603,272 control chromosomes in the GnomAD database, including 31,374 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 0.18 ( 3174 hom., cov: 32)

Exomes 𝑓: 0.18 ( 28200 hom. )

Consequence

PNPLA3
NM_025225.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.44

Publications

31 publications found

Variant links:

Genes affected

PNPLA3 (HGNC:18590): (patatin like phospholipase domain containing 3) The protein encoded by this gene is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. [provided by RefSeq, Jul 2008]

PNPLA3 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	NM_025225.3	MANE Select	c.487-28G>A		intron	N/A	NP_079501.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.487-28G>A	intron	N/A	ENSP00000216180.3	Q9NST1-1
PNPLA3	ENST00000862822.1		c.517-28G>A	intron	N/A	ENSP00000532881.1
PNPLA3	ENST00000862819.1		c.487-28G>A	intron	N/A	ENSP00000532878.1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28111

AN:

152094

Hom.:

3173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.193

GnomAD2 exomes

AF:

0.235

AC:

58931

AN:

250714

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.513

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.181

AC:

262672

AN:

1451060

Hom.:

28200

Cov.:

AF XY:

0.181

AC XY:

130652

AN XY:

722570

show subpopulations

African (AFR)

AF:

0.121

AC:

4010

AN:

33250

American (AMR)

AF:

0.496

AC:

22156

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4061

AN:

26064

East Asian (EAS)

AF:

0.417

AC:

16536

AN:

39628

South Asian (SAS)

AF:

0.207

AC:

17795

AN:

86016

European-Finnish (FIN)

AF:

0.192

AC:

10277

AN:

53396

Middle Eastern (MID)

AF:

0.188

AC:

1079

AN:

5754

European-Non Finnish (NFE)

AF:

0.160

AC:

176039

AN:

1102278

Other (OTH)

AF:

0.179

AC:

10719

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

11424

22848

34273

45697

57121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6424

12848

19272

25696

32120

<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:

0.185

AC:

28115

AN:

152212

Hom.:

3174

Cov.:

AF XY:

0.192

AC XY:

14272

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.126

AC:

5227

AN:

41538

American (AMR)

AF:

0.365

AC:

5575

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

529

AN:

3472

East Asian (EAS)

AF:

0.390

AC:

2020

AN:

5178

South Asian (SAS)

AF:

0.222

AC:

1069

AN:

4814

European-Finnish (FIN)

AF:

0.189

AC:

2003

AN:

10602

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11068

AN:

68006

Other (OTH)

AF:

0.192

AC:

405

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1140

2281

3421

4562

5702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.184

Hom.:

4868

Bravo

AF:

0.200

Asia WGS

AF:

0.287

AC:

994

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0050

(source)

DANN

Benign

0.48

PhyloP100

-4.4

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