rs761885395

Variant names:

• chr11-819883-G-A
• rs761885395
• NM_020376.4:c.165G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-819883-G-A
• chr11-819883-G-C
• chr11-819883-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_020376.4(PNPLA2):​c.165G>A​(p.Ala55Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000774 in 1,291,742 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. Synonymous variant affecting the same amino acid position (i.e. A55A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: PNPLA2 NM_020376.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• 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: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=-0.442 with no splicing effect.

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.165G>A	p.Ala55Ala	synonymous	Exon 2 of 10	NP_065109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	ENST00000336615.9	TSL:1 MANE Select	c.165G>A	p.Ala55Ala	synonymous	Exon 2 of 10	ENSP00000337701.4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.74e-7 AC: 1 AN: 1291742 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 632742

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26052

American (AMR) AF: 0.00 AC: 0 AN: 23144

Ashkenazi Jewish (ASJ) AF: 0.0000444 AC: 1 AN: 22510

East Asian (EAS) AF: 0.00 AC: 0 AN: 27534

South Asian (SAS) AF: 0.00 AC: 0 AN: 69668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4020

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1030928

Other (OTH) AF: 0.00 AC: 0 AN: 53294

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		-0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs761885395; hg19: chr11-819883;