rs7942159

Variant names:

• chr11-822622-A-G
• rs7942159
• NM_020376.4:c.696+16A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-822622-A-G
• chr11-822622-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020376.4(PNPLA2):​c.696+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,605,112 control chromosomes in the GnomAD database, including 261,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23921 hom., cov: 33)
  • Exomes 𝑓: 0.56 (237701 hom.)
• Consequence: PNPLA2 NM_020376.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.71
• Publications: 30 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-822622-A-G is Benign according to our data. Variant chr11-822622-A-G is described in ClinVar as Benign. ClinVar VariationId is 261245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.606 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.696+16A>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.696+16A>G		intron	N/A	ENSP00000337701.4
	PNPLA2	ENST00000525250.5	TSL:2	n.1302+16A>G		intron	N/A
	PNPLA2	ENST00000531923.1	TSL:2	n.591+16A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84234 AN: 151954 Hom.: 23880 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.538 AC: 134548 AN: 249872 AF XY: 0.519

Gnomad AFR exome AF: 0.516

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.291

Gnomad FIN exome AF: 0.659

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.564 AC: 819950 AN: 1453040 Hom.: 237701 Cov.: 30 AF XY: 0.555 AC XY: 401132 AN XY: 723400

African (AFR) AF: 0.516 AC: 17205 AN: 33318

American (AMR) AF: 0.686 AC: 30651 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 11798 AN: 26070

East Asian (EAS) AF: 0.326 AC: 12932 AN: 39650

South Asian (SAS) AF: 0.288 AC: 24773 AN: 86094

European-Finnish (FIN) AF: 0.655 AC: 34014 AN: 51896

Middle Eastern (MID) AF: 0.470 AC: 2694 AN: 5728

European-Non Finnish (NFE) AF: 0.591 AC: 653783 AN: 1105488

Other (OTH) AF: 0.534 AC: 32100 AN: 60090

GnomAD4 genome AF: 0.555 AC: 84328 AN: 152072 Hom.: 23921 Cov.: 33 AF XY: 0.552 AC XY: 41049 AN XY: 74336

African (AFR) AF: 0.513 AC: 21259 AN: 41464

American (AMR) AF: 0.617 AC: 9424 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1569 AN: 3472

East Asian (EAS) AF: 0.303 AC: 1568 AN: 5168

South Asian (SAS) AF: 0.287 AC: 1385 AN: 4824

European-Finnish (FIN) AF: 0.658 AC: 6960 AN: 10580

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40221 AN: 67966

Other (OTH) AF: 0.555 AC: 1170 AN: 2110

Alfa AF: 0.574 Hom.: 33225

Bravo AF: 0.554

Asia WGS AF: 0.337 AC: 1175 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Neutral lipid storage myopathy (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.81
PhyloP100		-1.7
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: rs7942159; hg19: chr11-822622; COSMIC: COSV60744661; COSMIC: COSV60744661;