Variant rs7942159 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020376.4(PNPLA2):c.696+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,605,112 control chromosomes in the GnomAD database, including 261,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23921 hom., cov: 33)

Exomes 𝑓: 0.56 ( 237701 hom. )

Consequence

PNPLA2
NM_020376.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.71

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-822622-A-G is Benign according to our data. Variant chr11-822622-A-G is described in ClinVar as [Benign]. Clinvar id is 261245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-822622-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA2	NM_020376.4 linkuse as main transcript	c.696+16A>G		intron_variant		ENST00000336615.9	NP_065109.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
PNPLA2	ENST00000336615.9 linkuse as main transcript	c.696+16A>G	intron_variant	1	NM_020376.4	ENSP00000337701	P1	Q96AD5-1
PNPLA2	ENST00000525250.5 linkuse as main transcript	n.1302+16A>G	intron_variant, non_coding_transcript_variant	2
PNPLA2	ENST00000531923.1 linkuse as main transcript	n.591+16A>G	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84234

AN:

151954

Hom.:

23880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.687

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.538

AC:

134548

AN:

249872

Hom.:

38826

AF XY:

0.519

AC XY:

70291

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.516

Gnomad AMR exome

AF:

0.694

Gnomad ASJ exome

AF:

0.452

Gnomad EAS exome

AF:

0.291

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.588

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.564

AC:

819950

AN:

1453040

Hom.:

237701

Cov.:

AF XY:

0.555

AC XY:

401132

AN XY:

723400

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.686

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.288

Gnomad4 FIN exome

AF:

0.655

Gnomad4 NFE exome

AF:

0.591

Gnomad4 OTH exome

AF:

0.534

GnomAD4 genome

AF:

0.555

AC:

84328

AN:

152072

Hom.:

23921

Cov.:

AF XY:

0.552

AC XY:

41049

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.513

Gnomad4 AMR

AF:

0.617

Gnomad4 ASJ

AF:

0.452

Gnomad4 EAS

AF:

0.303

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.658

Gnomad4 NFE

AF:

0.592

Gnomad4 OTH

AF:

0.555

Alfa

AF:

0.575

Hom.:

25664

Bravo

AF:

0.554

Asia WGS

AF:

0.337

AC:

1175

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Neutral lipid storage myopathy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over