11-819464-T-G

Position:

• chr11-819464-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA2	NM_020376.4	c.-145-110T>G		intron_variant		ENST00000336615.9	NP_065109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA2	ENST00000336615.9	c.-145-110T>G		intron_variant		1	NM_020376.4	ENSP00000337701	P1

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

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.486

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

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.480

Alfa AF: 0.527 Hom.: 2687

Bravo AF: 0.457

Asia WGS AF: 0.258 AC: 895 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs7928917; hg19: chr11-819464; COSMIC: COSV60745136; COSMIC: COSV60745136;