rs12196677

Positions:

• chr6-36258748-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000312917.9(PNPLA1):​c.-81+15487A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 152,230 control chromosomes in the GnomAD database, including 668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.086 (668 hom., cov: 32)
• Consequence: PNPLA1 ENST00000312917.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

Genes affected

PNPLA1 (HGNC:21246): (patatin like phospholipase domain containing 1) The protein encoded by this gene belongs to the patatin-like phospholipase (PNPLA) family, which is characterized by the presence of a highly conserved patatin domain. PNPLA family members have diverse lipolytic and acyltransferase activities, and are key elements in lipid metabolism. While other members of this family have been well characterized, the function of this gene remained an enigma. However, recent studies show that this gene is expressed in the skin epidermal keratinocytes, and has a role in glycerophospholipid metabolism in the cutaneous barrier. Consistent with these observations, mutations in this gene are associated with ichthyosis in human (autosomal recessive congenital ichthyoses, ARCI) and dog. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA1	NM_001145716.2	c.-81+15487A>G		intron_variant
PNPLA1	NM_173676.2	c.-81+15487A>G		intron_variant
PNPLA1	XM_011514520.3	c.-81+15487A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA1	ENST00000312917.9	c.-81+15487A>G		intron_variant		1
PNPLA1	ENST00000388715.7	c.-81+15487A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13140 AN: 152112 Hom.: 669 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0863 AC: 13141 AN: 152230 Hom.: 668 Cov.: 32 AF XY: 0.0826 AC XY: 6148 AN XY: 74416

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.0999

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0276

Gnomad4 SAS AF: 0.0417

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.116

Alfa AF: 0.114 Hom.: 1505

Bravo AF: 0.0914

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs12196677; hg19: chr6-36226525;