rs2896019

Variant names:

• chr22-43937814-T-G
• rs2896019
• NM_025225.3:c.979+542T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025225.3(PNPLA3):​c.979+542T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,150 control chromosomes in the GnomAD database, including 3,673 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 (3673 hom., cov: 32)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 53 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	NM_025225.3	MANE Select	c.979+542T>G		intron	N/A	NP_079501.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.979+542T>G		intron	N/A	ENSP00000216180.3	Q9NST1-1
	PNPLA3	ENST00000862822.1		c.1009+542T>G		intron	N/A	ENSP00000532881.1
	PNPLA3	ENST00000862819.1		c.1003+542T>G		intron	N/A	ENSP00000532878.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30943 AN: 152032 Hom.: 3673 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.203 AC: 30950 AN: 152150 Hom.: 3673 Cov.: 32 AF XY: 0.211 AC XY: 15701 AN XY: 74386

African (AFR) AF: 0.165 AC: 6870 AN: 41522

American (AMR) AF: 0.376 AC: 5739 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2038 AN: 5152

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10578

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11585 AN: 68018

Other (OTH) AF: 0.208 AC: 438 AN: 2108

Alfa AF: 0.188 Hom.: 13173

Bravo AF: 0.217

Asia WGS AF: 0.292 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.73
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2896019; hg19: chr22-44333694;