chr22-43936690-G-A

Variant names:

• chr22-43936690-G-A
• rs2281135
• NM_025225.3:c.758-361G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025225.3(PNPLA3):​c.758-361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,140 control chromosomes in the GnomAD database, including 3,520 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 (3520 hom., cov: 32)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 71 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	NM_025225.3	MANE Select	c.758-361G>A		intron	N/A	NP_079501.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.758-361G>A		intron	N/A	ENSP00000216180.3	Q9NST1-1
	PNPLA3	ENST00000862822.1		c.788-361G>A		intron	N/A	ENSP00000532881.1
	PNPLA3	ENST00000862819.1		c.782-361G>A		intron	N/A	ENSP00000532878.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30105 AN: 152022 Hom.: 3519 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.198 AC: 30114 AN: 152140 Hom.: 3520 Cov.: 32 AF XY: 0.206 AC XY: 15324 AN XY: 74362

African (AFR) AF: 0.147 AC: 6117 AN: 41526

American (AMR) AF: 0.373 AC: 5693 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3468

East Asian (EAS) AF: 0.392 AC: 2020 AN: 5156

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2430 AN: 10580

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

European-Non Finnish (NFE) AF: 0.170 AC: 11570 AN: 67984

Other (OTH) AF: 0.204 AC: 432 AN: 2116

Alfa AF: 0.190 Hom.: 12820

Bravo AF: 0.211

Asia WGS AF: 0.290 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.081
DANN	Benign	0.45
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2281135; hg19: chr22-44332570;