Variant chr22-43924110-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025225.3(PNPLA3):c.187+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,529,776 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 44 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 36 hom. )

Consequence

PNPLA3
NM_025225.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.895

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 22-43924110-G-A is Benign according to our data. Variant chr22-43924110-G-A is described in ClinVar as [Benign]. Clinvar id is 341926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1614/152368) while in subpopulation AFR AF= 0.0371 (1542/41588). AF 95% confidence interval is 0.0355. There are 44 homozygotes in gnomad4. There are 769 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA3	NM_025225.3 linkuse as main transcript	c.187+12G>A		intron_variant		ENST00000216180.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PNPLA3	ENST00000216180.8 linkuse as main transcript	c.187+12G>A	intron_variant	1	NM_025225.3	P1	Q9NST1-1
PNPLA3	ENST00000423180.2 linkuse as main transcript	c.175+24G>A	intron_variant	2			Q9NST1-2
PNPLA3	ENST00000406117.6 linkuse as main transcript	c.187+12G>A	intron_variant, NMD_transcript_variant	2
PNPLA3	ENST00000478713.1 linkuse as main transcript		upstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1604

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00251

AC:

390

AN:

155330

Hom.:

AF XY:

0.00168

AC XY:

149

AN XY:

88918

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.000141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000442

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000235

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.00120

AC:

1654

AN:

1377408

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

758

AN XY:

682326

show subpopulations

Gnomad4 AFR exome

AF:

0.0436

Gnomad4 AMR exome

AF:

0.00223

Gnomad4 ASJ exome

AF:

0.0000417

Gnomad4 EAS exome

AF:

0.0000610

Gnomad4 SAS exome

AF:

0.0000890

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000145

Gnomad4 OTH exome

AF:

0.00281

GnomAD4 genome

AF:

0.0106

AC:

1614

AN:

152368

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

769

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0371

Gnomad4 AMR

AF:

0.00287

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00205

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00867

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NAFLD1

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.2

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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