rs2072906

Positions:

• chr22-43937292-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025225.3(PNPLA3):​c.979+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,602,366 control chromosomes in the GnomAD database, including 33,624 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 0.20 (3664 hom., cov: 33)
  • Exomes 𝑓: 0.19 (29960 hom.)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.979+20A>G		intron_variant		ENST00000216180.8	NP_079501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8	c.979+20A>G		intron_variant		1	NM_025225.3	ENSP00000216180.3
PNPLA3	ENST00000423180.2	c.967+20A>G		intron_variant		2		ENSP00000397987.2
PNPLA3	ENST00000406117.6	n.*611+20A>G		intron_variant		2		ENSP00000384668.2
PNPLA3	ENST00000497129.1	n.364+20A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30910 AN: 152024 Hom.: 3664 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.247 AC: 60247 AN: 244280 Hom.: 9491 AF XY: 0.234 AC XY: 30969 AN XY: 132308

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.391

Gnomad SAS exome AF: 0.208

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.189 AC: 274362 AN: 1450224 Hom.: 29960 Cov.: 30 AF XY: 0.189 AC XY: 136126 AN XY: 721514

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.203 AC: 30917 AN: 152142 Hom.: 3664 Cov.: 33 AF XY: 0.211 AC XY: 15698 AN XY: 74380

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.206

Alfa AF: 0.180 Hom.: 722

Bravo AF: 0.217

Asia WGS AF: 0.292 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.028
DANN	Benign	0.23

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

Other links and lift over

dbSNP: rs2072906; hg19: chr22-44333172; COSMIC: COSV53380679; COSMIC: COSV53380679;