NM_020376.4:c.-145-110T>G

Variant names:

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

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.-145-110T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,189,408 control chromosomes in the GnomAD database, including 174,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (18213 hom., cov: 35)
  • Exomes 𝑓: 0.54 (156665 hom.)
• Consequence: PNPLA2 NM_020376.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.124
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 11-819464-T-G is Benign according to our data. Variant chr11-819464-T-G is described in ClinVar as Benign. ClinVar VariationId is 1250739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 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.-145-110T>G		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>G		intron	N/A	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000869283.1		c.-145-110T>G		intron	N/A	ENSP00000539342.1
	PNPLA2	ENST00000869284.1		c.-145-110T>G		intron	N/A	ENSP00000539343.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70574 AN: 151850 Hom.: 18199 Cov.: 35

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.542 AC: 562762 AN: 1037452 Hom.: 156665 Cov.: 19 AF XY: 0.540 AC XY: 265256 AN XY: 491646

African (AFR) AF: 0.254 AC: 5353 AN: 21072

American (AMR) AF: 0.626 AC: 4097 AN: 6548

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 5258 AN: 12848

East Asian (EAS) AF: 0.297 AC: 6493 AN: 21834

South Asian (SAS) AF: 0.221 AC: 6001 AN: 27116

European-Finnish (FIN) AF: 0.620 AC: 12223 AN: 19714

Middle Eastern (MID) AF: 0.432 AC: 1159 AN: 2680

European-Non Finnish (NFE) AF: 0.568 AC: 502392 AN: 884968

Other (OTH) AF: 0.486 AC: 19786 AN: 40672

GnomAD4 genome AF: 0.465 AC: 70610 AN: 151956 Hom.: 18213 Cov.: 35 AF XY: 0.462 AC XY: 34350 AN XY: 74272

African (AFR) AF: 0.265 AC: 10989 AN: 41438

American (AMR) AF: 0.578 AC: 8844 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3464

East Asian (EAS) AF: 0.253 AC: 1292 AN: 5108

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4828

European-Finnish (FIN) AF: 0.620 AC: 6575 AN: 10604

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38601 AN: 67896

Other (OTH) AF: 0.480 AC: 1016 AN: 2116

Alfa AF: 0.527 Hom.: 2687

Bravo AF: 0.457

Asia WGS AF: 0.258 AC: 895 AN: 3458

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.12
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: rs7928917; hg19: chr11-819464; COSMIC: COSV60745136; COSMIC: COSV60745136;