rs2076211

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-43933198-C-A
• chr22-43933198-C-G
• chr22-43933198-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025225.3(PNPLA3):​c.696+111C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000585 in 1,025,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000057 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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>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.696+111C>A		intron	N/A	ENSP00000216180.3
	PNPLA3	ENST00000862822.1		c.726+111C>A		intron	N/A	ENSP00000532881.1
	PNPLA3	ENST00000862819.1		c.696+111C>A		intron	N/A	ENSP00000532878.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151852 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000572 AC: 5 AN: 873992 Hom.: 0 AF XY: 0.00000445 AC XY: 2 AN XY: 448942

African (AFR) AF: 0.00 AC: 0 AN: 21058

American (AMR) AF: 0.00 AC: 0 AN: 33470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18534

East Asian (EAS) AF: 0.00 AC: 0 AN: 36702

South Asian (SAS) AF: 0.00 AC: 0 AN: 63148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2854

European-Non Finnish (NFE) AF: 0.00000807 AC: 5 AN: 619570

Other (OTH) AF: 0.00 AC: 0 AN: 40468

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151970 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74244

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		0.096

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;