rs7928917

Variant names:

• chr11-819464-T-C
• rs7928917
• NM_020376.4:c.-145-110T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-819464-T-C
• chr11-819464-T-G

Variant summary

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

The NM_020376.4(PNPLA2):​c.-145-110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000096 in 1,042,078 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: not found (cov: 35)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
• Consequence: PNPLA2 NM_020376.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 0 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: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

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=-0.69).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	NM_020376.4	MANE Select	c.-145-110T>C		intron	N/A	NP_065109.1	Q96AD5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	ENST00000336615.9	TSL:1 MANE Select	c.-145-110T>C		intron	N/A	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000869283.1		c.-145-110T>C		intron	N/A	ENSP00000539342.1
	PNPLA2	ENST00000869284.1		c.-145-110T>C		intron	N/A	ENSP00000539343.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 9.60e-7 AC: 1 AN: 1042078 Hom.: 0 Cov.: 19 AF XY: 0.00000202 AC XY: 1 AN XY: 493840

African (AFR) AF: 0.00 AC: 0 AN: 21152

American (AMR) AF: 0.00 AC: 0 AN: 6592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12910

East Asian (EAS) AF: 0.0000457 AC: 1 AN: 21896

South Asian (SAS) AF: 0.00 AC: 0 AN: 27246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 888928

Other (OTH) AF: 0.00 AC: 0 AN: 40872

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.12

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: rs7928917; hg19: chr11-819464;