rs12483959

Positions:

• chr22-43930116-G-A
• chr22-43930116-G-C
• chr22-43930116-G-T

Variant summary

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

The NM_025225.3(PNPLA3):​c.486+1227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,088 control chromosomes in the GnomAD database, including 3,159 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 (3159 hom., cov: 32)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.486+1227G>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.486+1227G>A		intron_variant		1	NM_025225.3	ENSP00000216180	P1
PNPLA3	ENST00000423180.2	c.474+1227G>A		intron_variant		2		ENSP00000397987
PNPLA3	ENST00000406117.6	c.*118+1227G>A		intron_variant, NMD_transcript_variant		2		ENSP00000384668
PNPLA3	ENST00000478713.1	n.520+1227G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27982 AN: 151970 Hom.: 3157 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.184 AC: 27986 AN: 152088 Hom.: 3159 Cov.: 32 AF XY: 0.191 AC XY: 14209 AN XY: 74370

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.192

Alfa AF: 0.157 Hom.: 1311

Bravo AF: 0.199

Asia WGS AF: 0.281 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.61

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: rs12483959; hg19: chr22-44325996;