rs4823173

Positions:

• chr22-43932850-G-A

Variant summary

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

The ENST00000216180.8(PNPLA3):​c.487-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,603,272 control chromosomes in the GnomAD database, including 31,374 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 0.18 (3174 hom., cov: 32)
  • Exomes 𝑓: 0.18 (28200 hom.)
• Consequence: PNPLA3 ENST00000216180.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.44

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.487-28G>A		intron_variant		ENST00000216180.8	NP_079501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8	c.487-28G>A		intron_variant		1	NM_025225.3	ENSP00000216180	P1
PNPLA3	ENST00000423180.2	c.475-28G>A		intron_variant		2		ENSP00000397987
PNPLA3	ENST00000406117.6	c.*119-28G>A		intron_variant, NMD_transcript_variant		2		ENSP00000384668
PNPLA3	ENST00000478713.1	n.521-28G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28111 AN: 152094 Hom.: 3173 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.235 AC: 58931 AN: 250714 Hom.: 9331 AF XY: 0.223 AC XY: 30249 AN XY: 135518

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.513

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.387

Gnomad SAS exome AF: 0.205

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.181 AC: 262672 AN: 1451060 Hom.: 28200 Cov.: 29 AF XY: 0.181 AC XY: 130652 AN XY: 722570

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.185 AC: 28115 AN: 152212 Hom.: 3174 Cov.: 32 AF XY: 0.192 AC XY: 14272 AN XY: 74424

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.192

Alfa AF: 0.180 Hom.: 2992

Bravo AF: 0.200

Asia WGS AF: 0.287 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0050
DANN	Benign	0.48

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: rs4823173; hg19: chr22-44328730; COSMIC: COSV53377686; COSMIC: COSV53377686;