22-43933198-C-T

Variant names:

• chr22-43933198-C-T
• rs2076211
• NM_025225.3:c.696+111C>T

Variant summary

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

The NM_025225.3(PNPLA3):​c.696+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,024,752 control chromosomes in the GnomAD database, including 22,126 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 (3162 hom., cov: 31)
  • Exomes 𝑓: 0.19 (18964 hom.)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 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.696+111C>T		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.696+111C>T		intron	N/A	ENSP00000216180.3
	PNPLA3	ENST00000862822.1		c.726+111C>T		intron	N/A	ENSP00000532881.1
	PNPLA3	ENST00000862819.1		c.696+111C>T		intron	N/A	ENSP00000532878.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28035 AN: 151780 Hom.: 3160 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.189 AC: 165282 AN: 872854 Hom.: 18964 AF XY: 0.189 AC XY: 84696 AN XY: 448372

African (AFR) AF: 0.124 AC: 2620 AN: 21046

American (AMR) AF: 0.497 AC: 16617 AN: 33406

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 2942 AN: 18516

East Asian (EAS) AF: 0.420 AC: 15393 AN: 36672

South Asian (SAS) AF: 0.211 AC: 13287 AN: 63096

European-Finnish (FIN) AF: 0.192 AC: 7318 AN: 38152

Middle Eastern (MID) AF: 0.179 AC: 509 AN: 2848

European-Non Finnish (NFE) AF: 0.160 AC: 99182 AN: 618680

Other (OTH) AF: 0.183 AC: 7414 AN: 40438

GnomAD4 genome AF: 0.185 AC: 28041 AN: 151898 Hom.: 3162 Cov.: 31 AF XY: 0.191 AC XY: 14207 AN XY: 74206

African (AFR) AF: 0.126 AC: 5208 AN: 41444

American (AMR) AF: 0.365 AC: 5565 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.389 AC: 2000 AN: 5144

South Asian (SAS) AF: 0.221 AC: 1059 AN: 4798

European-Finnish (FIN) AF: 0.189 AC: 1995 AN: 10534

Middle Eastern (MID) AF: 0.155 AC: 45 AN: 290

European-Non Finnish (NFE) AF: 0.163 AC: 11061 AN: 67966

Other (OTH) AF: 0.193 AC: 407 AN: 2108

Alfa AF: 0.177 Hom.: 1574

Bravo AF: 0.200

Asia WGS AF: 0.287 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.47
PhyloP100		0.096
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: rs2076211; hg19: chr22-44329078; COSMIC: COSV53379317; COSMIC: COSV53379317;