rs12212459

Positions:

• chr6-36284427-C-A

Variant summary

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

The NM_001374623.1(PNPLA1):​c.206-6893C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,014 control chromosomes in the GnomAD database, including 28,192 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 0.61 (28192 hom., cov: 31)
• Consequence: PNPLA1 NM_001374623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA1	NM_001374623.1	c.206-6893C>A		intron_variant		ENST00000636260.2	NP_001361552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA1	ENST00000636260.2	c.206-6893C>A		intron_variant		5	NM_001374623.1	ENSP00000490785	A2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92403 AN: 151896 Hom.: 28169 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.608 AC: 92469 AN: 152014 Hom.: 28192 Cov.: 31 AF XY: 0.604 AC XY: 44862 AN XY: 74300

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.662

Alfa AF: 0.608 Hom.: 6491

Bravo AF: 0.621

Asia WGS AF: 0.636 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.024
DANN	Benign	0.61

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: rs12212459; hg19: chr6-36252204;