rs2072907

Positions:

• chr22-43936773-C-G

Variant summary

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

The NM_025225.3(PNPLA3):​c.758-278C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,158 control chromosomes in the GnomAD database, including 3,581 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 (3581 hom., cov: 32)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.72

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 = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.758-278C>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.758-278C>G		intron_variant		1	NM_025225.3	ENSP00000216180.3
PNPLA3	ENST00000423180.2	c.746-278C>G		intron_variant		2		ENSP00000397987.2
PNPLA3	ENST00000406117.6	n.*390-278C>G		intron_variant		2		ENSP00000384668.2
PNPLA3	ENST00000497129.1	n.143-278C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30388 AN: 152040 Hom.: 3579 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.200 AC: 30397 AN: 152158 Hom.: 3581 Cov.: 32 AF XY: 0.208 AC XY: 15471 AN XY: 74368

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.206

Alfa AF: 0.185 Hom.: 371

Bravo AF: 0.212

Asia WGS AF: 0.290 AC: 1006 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	0.0020
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: rs2072907; hg19: chr22-44332653;