dbSNP rs12270408: PNPLA2:c.696+91G>C (chr11-822697-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_020376.4(PNPLA2):c.696+91G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,128,920 control chromosomes in the GnomAD database, including 1 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 0.00054 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

PNPLA2
NM_020376.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.138

Publications

1 publications found

Variant links:

Genes affected

PNPLA2 (HGNC:30802): (patatin like phospholipase domain containing 2) This gene encodes an enzyme which catalyzes the first step in the hydrolysis of triglycerides in adipose tissue. Mutations in this gene are associated with neutral lipid storage disease with myopathy. [provided by RefSeq, Jul 2010]

PNPLA2 Gene-Disease associations (from GenCC):

neutral lipid storage myopathy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

PNPLA2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_020376.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000538 (82/152368) while in subpopulation AFR AF = 0.00192 (80/41586). AF 95% confidence interval is 0.00158. There are 0 homozygotes in GnomAd4. There are 31 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020376.4. 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
	PNPLA2	NM_020376.4	MANE Select	c.696+91G>C		intron	N/A	NP_065109.1	Q96AD5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PNPLA2	ENST00000336615.9	TSL:1 MANE Select	c.696+91G>C	intron	N/A	ENSP00000337701.4	Q96AD5-1
PNPLA2	ENST00000869283.1		c.1080+91G>C	intron	N/A	ENSP00000539342.1
PNPLA2	ENST00000869284.1		c.696+91G>C	intron	N/A	ENSP00000539343.1

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

100

AN:

976552

Hom.:

AF XY:

0.0000793

AC XY:

AN XY:

504530

show subpopulations

African (AFR)

AF:

0.00319

AC:

AN:

24102

American (AMR)

AF:

0.000255

AC:

AN:

43220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23044

East Asian (EAS)

AF:

0.00

AC:

AN:

36892

South Asian (SAS)

AF:

0.0000263

AC:

AN:

76082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3638

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

685074

Other (OTH)

AF:

0.000225

AC:

AN:

44480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000538

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00192

AC:

AN:

41586

American (AMR)

AF:

0.000131

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000485

Hom.:

Bravo

AF:

0.000869

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.39

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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