rs145835771

chr11-823603-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_020376.4(PNPLA2):c.757+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000939 in 1,134,754 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (6 hom.)
• Consequence: PNPLA2 NM_020376.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.841

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-823603-C-T is Benign according to our data. Variant chr11-823603-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-823603-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000586 (85/144936) while in subpopulation SAS AF= 0.00147 (6/4074). AF 95% confidence interval is 0.000641. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA2	NM_020376.4	c.757+16C>T		intron_variant		ENST00000336615.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA2	ENST00000336615.9	c.757+16C>T		intron_variant		1	NM_020376.4	P1
	ENST00000532946.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.000594 AC: 86 AN: 144784 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000612

Gnomad ASJ AF: 0.00479

Gnomad EAS AF: 0.000230

Gnomad SAS AF: 0.00148

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.000579

Gnomad OTH AF: 0.00147

GnomAD3 exomes AF: 0.000772 AC: 180 AN: 233228 Hom.: 0 AF XY: 0.000858 AC XY: 109 AN XY: 127056

Gnomad AFR exome AF: 0.000141

Gnomad AMR exome AF: 0.000180

Gnomad ASJ exome AF: 0.00374

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000750

Gnomad OTH exome AF: 0.00105

GnomAD4 exome AF: 0.000991 AC: 981 AN: 989818 Hom.: 6 Cov.: 34 AF XY: 0.00104 AC XY: 523 AN XY: 505056

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00448

Gnomad4 EAS exome AF: 0.0000334

Gnomad4 SAS exome AF: 0.00212

Gnomad4 FIN exome AF: 0.000123

Gnomad4 NFE exome AF: 0.000906

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.000586 AC: 85 AN: 144936 Hom.: 0 Cov.: 32 AF XY: 0.000722 AC XY: 51 AN XY: 70680

Gnomad4 AFR AF: 0.000223

Gnomad4 AMR AF: 0.000611

Gnomad4 ASJ AF: 0.00479

Gnomad4 EAS AF: 0.000231

Gnomad4 SAS AF: 0.00147

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000579

Gnomad4 OTH AF: 0.00145

Alfa AF: 0.000897 Hom.: 0

Bravo AF: 0.000450

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Neutral lipid storage myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	12
Dann	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145835771; hg19: chr11-823603;