rs7925131

Variant names:

• chr11-820268-A-G
• rs7925131
• NM_020376.4:c.187+363A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-820268-A-G
• chr11-820268-A-T

Variant summary

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

The NM_020376.4(PNPLA2):​c.187+363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,178 control chromosomes in the GnomAD database, including 38,548 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 0.71 (38548 hom., cov: 34)
• Consequence: PNPLA2 NM_020376.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 13 publications found

Genes affected

PNPLA2 (HGNC:30802): (patatin like phospholipase domain containing 2) This gene encodes an enzyme which catalyzes the first step in the hydrolysis of triglycerides in adipose tissue. Mutations in this gene are associated with neutral lipid storage disease with myopathy. [provided by RefSeq, Jul 2010]

PNPLA2 Gene-Disease associations (from GenCC):

• neutral lipid storage myopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020376.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	NM_020376.4	MANE Select	c.187+363A>G		intron	N/A	NP_065109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	ENST00000336615.9	TSL:1 MANE Select	c.187+363A>G		intron	N/A	ENSP00000337701.4

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107679 AN: 152060 Hom.: 38486 Cov.: 34

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.708 AC: 107798 AN: 152178 Hom.: 38548 Cov.: 34 AF XY: 0.702 AC XY: 52262 AN XY: 74404

African (AFR) AF: 0.718 AC: 29820 AN: 41518

American (AMR) AF: 0.738 AC: 11290 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3146 AN: 5162

South Asian (SAS) AF: 0.502 AC: 2421 AN: 4822

European-Finnish (FIN) AF: 0.714 AC: 7568 AN: 10596

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49375 AN: 67988

Other (OTH) AF: 0.687 AC: 1453 AN: 2114

Alfa AF: 0.715 Hom.: 24196

Bravo AF: 0.710

Asia WGS AF: 0.598 AC: 2080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		-0.23
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs7925131; hg19: chr11-820268;