rs1138694

Variant names:

• chr11-824805-C-T
• rs1138694
• NM_020376.4:c.1458C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-824805-C-T
• chr11-824805-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020376.4(PNPLA2):​c.1458C>T​(p.Pro486Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,534,204 control chromosomes in the GnomAD database, including 27,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4324 hom., cov: 34)
  • Exomes 𝑓: 0.18 (23211 hom.)
• Consequence: PNPLA2 NM_020376.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.511
• Publications: 15 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, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ENSG00000255108 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-824805-C-T is Benign according to our data. Variant chr11-824805-C-T is described in ClinVar as Benign. ClinVar VariationId is 261238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.511 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	NM_020376.4	MANE Select	c.1458C>T	p.Pro486Pro	synonymous	Exon 10 of 10	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.1458C>T	p.Pro486Pro	synonymous	Exon 10 of 10	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000529255.1	TSL:1	n.888C>T		non_coding_transcript_exon	Exon 4 of 4
	PNPLA2	ENST00000869283.1		c.1842C>T	p.Pro614Pro	synonymous	Exon 11 of 11	ENSP00000539342.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32684 AN: 152100 Hom.: 4295 Cov.: 34

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.183 AC: 23580 AN: 128670 AF XY: 0.188

Gnomad AFR exome AF: 0.371

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.326

Gnomad FIN exome AF: 0.0906

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.176 AC: 243905 AN: 1381988 Hom.: 23211 Cov.: 38 AF XY: 0.178 AC XY: 121455 AN XY: 682088

African (AFR) AF: 0.362 AC: 11397 AN: 31474

American (AMR) AF: 0.106 AC: 3748 AN: 35500

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3154 AN: 25024

East Asian (EAS) AF: 0.312 AC: 11133 AN: 35716

South Asian (SAS) AF: 0.252 AC: 19973 AN: 79150

European-Finnish (FIN) AF: 0.101 AC: 3389 AN: 33692

Middle Eastern (MID) AF: 0.101 AC: 572 AN: 5688

European-Non Finnish (NFE) AF: 0.167 AC: 179824 AN: 1077954

Other (OTH) AF: 0.185 AC: 10715 AN: 57790

GnomAD4 genome AF: 0.215 AC: 32749 AN: 152216 Hom.: 4324 Cov.: 34 AF XY: 0.212 AC XY: 15792 AN XY: 74426

African (AFR) AF: 0.356 AC: 14786 AN: 41518

American (AMR) AF: 0.146 AC: 2239 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1629 AN: 5164

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4822

European-Finnish (FIN) AF: 0.0917 AC: 974 AN: 10626

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10890 AN: 67982

Other (OTH) AF: 0.188 AC: 397 AN: 2116

Alfa AF: 0.172 Hom.: 482

Bravo AF: 0.221

Asia WGS AF: 0.318 AC: 1105 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Neutral lipid storage myopathy (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.87
PhyloP100		-0.51
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: rs1138694; hg19: chr11-824805; COSMIC: COSV60743956; COSMIC: COSV60743956;