rs2072906

Variant names:

• chr22-43937292-A-G
• rs2072906
• NM_025225.3:c.979+20A>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+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,602,366 control chromosomes in the GnomAD database, including 33,624 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 (3664 hom., cov: 33)
  • Exomes 𝑓: 0.19 (29960 hom.)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.979+20A>G		intron_variant	Intron 6 of 8	ENST00000216180.8	NP_079501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8	c.979+20A>G		intron_variant	Intron 6 of 8	1	NM_025225.3	ENSP00000216180.3
PNPLA3	ENST00000423180.2	c.967+20A>G		intron_variant	Intron 6 of 8	2		ENSP00000397987.2
PNPLA3	ENST00000406117.6	n.*611+20A>G		intron_variant	Intron 6 of 9	2		ENSP00000384668.2
PNPLA3	ENST00000497129.1	n.364+20A>G		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30910 AN: 152024 Hom.: 3664 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.247 AC: 60247 AN: 244280 AF XY: 0.234

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.391

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.189 AC: 274362 AN: 1450224 Hom.: 29960 Cov.: 30 AF XY: 0.189 AC XY: 136126 AN XY: 721514

African (AFR) AF: 0.166 AC: 5514 AN: 33290

American (AMR) AF: 0.497 AC: 21994 AN: 44256

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4233 AN: 26012

East Asian (EAS) AF: 0.419 AC: 16568 AN: 39564

South Asian (SAS) AF: 0.210 AC: 18004 AN: 85910

European-Finnish (FIN) AF: 0.230 AC: 11775 AN: 51242

Middle Eastern (MID) AF: 0.194 AC: 1079 AN: 5572

European-Non Finnish (NFE) AF: 0.167 AC: 183936 AN: 1104374

Other (OTH) AF: 0.188 AC: 11259 AN: 60004

GnomAD4 genome AF: 0.203 AC: 30917 AN: 152142 Hom.: 3664 Cov.: 33 AF XY: 0.211 AC XY: 15698 AN XY: 74380

African (AFR) AF: 0.166 AC: 6874 AN: 41528

American (AMR) AF: 0.374 AC: 5718 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 553 AN: 3466

East Asian (EAS) AF: 0.394 AC: 2030 AN: 5154

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

European-Finnish (FIN) AF: 0.231 AC: 2445 AN: 10600

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

European-Non Finnish (NFE) AF: 0.170 AC: 11566 AN: 67984

Other (OTH) AF: 0.206 AC: 435 AN: 2108

Alfa AF: 0.179 Hom.: 728

Bravo AF: 0.217

Asia WGS AF: 0.292 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.028
DANN	Benign	0.23
PhyloP100		-1.5
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: rs2072906; hg19: chr22-44333172; COSMIC: COSV53380679; COSMIC: COSV53380679;