22-43941653-G-A

Position:

• chr22-43941653-G-A

Variant summary

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

The NM_025225.3(PNPLA3):​c.1112+1528G>A 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 152,030 control chromosomes in the GnomAD database, including 3,649 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 (3649 hom., cov: 31)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA3	NM_025225.3	c.1112+1528G>A		intron_variant		ENST00000216180.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA3	ENST00000216180.8	c.1112+1528G>A		intron_variant		1	NM_025225.3	P1
PNPLA3	ENST00000423180.2	c.1100+1528G>A		intron_variant		2
PNPLA3	ENST00000406117.6	c.*744+1528G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30830 AN: 151912 Hom.: 3648 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.203 AC: 30838 AN: 152030 Hom.: 3649 Cov.: 31 AF XY: 0.211 AC XY: 15642 AN XY: 74292

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.205

Alfa AF: 0.181 Hom.: 1278

Bravo AF: 0.217

Asia WGS AF: 0.291 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.81

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: rs926633; hg19: chr22-44337533;