NM_025225.3:c.758-278C>G

Variant names:

• chr22-43936773-C-G
• rs2072907
• NM_025225.3:c.758-278C>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.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
• Publications: 8 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=-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 rank	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.758-278C>G		intron_variant	Intron 5 of 8	ENST00000216180.8	NP_079501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8	c.758-278C>G		intron_variant	Intron 5 of 8	1	NM_025225.3	ENSP00000216180.3
PNPLA3	ENST00000423180.2	c.746-278C>G		intron_variant	Intron 5 of 8	2		ENSP00000397987.2
PNPLA3	ENST00000406117.6	n.*390-278C>G		intron_variant	Intron 5 of 9	2		ENSP00000384668.2
PNPLA3	ENST00000497129.1	n.143-278C>G		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.148 AC: 6144 AN: 41512

American (AMR) AF: 0.373 AC: 5698 AN: 15290

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

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5166

South Asian (SAS) AF: 0.224 AC: 1077 AN: 4818

European-Finnish (FIN) AF: 0.237 AC: 2506 AN: 10576

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

European-Non Finnish (NFE) AF: 0.172 AC: 11730 AN: 68010

Other (OTH) AF: 0.206 AC: 435 AN: 2110

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
PhyloP100		-5.7
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: rs2072907; hg19: chr22-44332653;