rs543276875

Variant names:

• chr11-819526-G-A
• rs543276875
• NM_020376.4:c.-145-48G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-819526-G-A
• chr11-819526-G-C
• chr11-819526-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020376.4(PNPLA2):​c.-145-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,264,470 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 35)
  • Exomes 𝑓: 0.00030 (3 hom.)
• Consequence: PNPLA2 NM_020376.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.808
• Publications: 0 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: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-819526-G-A is Benign according to our data. Variant chr11-819526-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1326729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00294 (447/152274) while in subpopulation AFR AF = 0.0104 (434/41576). AF 95% confidence interval is 0.00963. There are 0 homozygotes in GnomAd4. There are 228 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.-145-48G>A		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.-145-48G>A		intron	N/A	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000869286.1		c.-193G>A		5_prime_UTR	Exon 1 of 9	ENSP00000539345.1
	PNPLA2	ENST00000869283.1		c.-145-48G>A		intron	N/A	ENSP00000539342.1

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 449 AN: 152164 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000301 AC: 335 AN: 1112196 Hom.: 3 Cov.: 28 AF XY: 0.000234 AC XY: 124 AN XY: 530754

African (AFR) AF: 0.0118 AC: 264 AN: 22328

American (AMR) AF: 0.000257 AC: 2 AN: 7780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14472

East Asian (EAS) AF: 0.00 AC: 0 AN: 24728

South Asian (SAS) AF: 0.0000574 AC: 2 AN: 34830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24628

Middle Eastern (MID) AF: 0.000338 AC: 1 AN: 2960

European-Non Finnish (NFE) AF: 0.0000267 AC: 25 AN: 935820

Other (OTH) AF: 0.000918 AC: 41 AN: 44650

GnomAD4 genome AF: 0.00294 AC: 447 AN: 152274 Hom.: 0 Cov.: 35 AF XY: 0.00306 AC XY: 228 AN XY: 74452

African (AFR) AF: 0.0104 AC: 434 AN: 41576

American (AMR) AF: 0.000588 AC: 9 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67986

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.00333

Asia WGS AF: 0.000290 AC: 1 AN: 3464

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.6
DANN	Benign	0.88
PhyloP100		-0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs543276875; hg19: chr11-819526;