11-824428-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020376.4(PNPLA2):c.1167G>T(p.Leu389=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,554,754 control chromosomes in the GnomAD database, including 2,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 246 hom., cov: 33)

Exomes 𝑓: 0.021 ( 1838 hom. )

Consequence

PNPLA2
NM_020376.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0150

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 11-824428-G-T is Benign according to our data. Variant chr11-824428-G-T is described in ClinVar as [Benign]. Clinvar id is 261231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.015 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA2	NM_020376.4 linkuse as main transcript	c.1167G>T	p.Leu389=	synonymous_variant	9/10	ENST00000336615.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA2	ENST00000336615.9 linkuse as main transcript	c.1167G>T	p.Leu389=	synonymous_variant	9/10	1	NM_020376.4	P1	Q96AD5-1
	ENST00000532946.1 linkuse as main transcript	n.307-565C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4886

AN:

152162

Hom.:

246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0440

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00727

Gnomad OTH

AF:

0.0277

GnomAD3 exomes

AF:

0.0470

AC:

7073

AN:

150510

Hom.:

559

AF XY:

0.0508

AC XY:

4124

AN XY:

81134

show subpopulations

Gnomad AFR exome

AF:

0.0454

Gnomad AMR exome

AF:

0.0148

Gnomad ASJ exome

AF:

0.0257

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.00197

Gnomad NFE exome

AF:

0.00734

Gnomad OTH exome

AF:

0.0311

GnomAD4 exome

AF:

0.0213

AC:

29899

AN:

1402474

Hom.:

1838

Cov.:

AF XY:

0.0240

AC XY:

16587

AN XY:

692332

show subpopulations

Gnomad4 AFR exome

AF:

0.0454

Gnomad4 AMR exome

AF:

0.0159

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.00228

Gnomad4 NFE exome

AF:

0.00690

Gnomad4 OTH exome

AF:

0.0353

GnomAD4 genome

AF:

0.0322

AC:

4905

AN:

152280

Hom.:

246

Cov.:

AF XY:

0.0353

AC XY:

2629

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0444

Gnomad4 AMR

AF:

0.0352

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.237

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00727

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0172

Hom.:

152

Bravo

AF:

0.0320

Asia WGS

AF:

0.164

AC:

571

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neutral lipid storage myopathy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

1.9

Dann

Benign

0.73

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