6-36262887-A-C

Position:

• chr6-36262887-A-C

Variant summary

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

The ENST00000312917.9(PNPLA1):​c.-81+19626A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,124 control chromosomes in the GnomAD database, including 14,080 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 0.42 (14080 hom., cov: 33)
• Consequence: PNPLA1 ENST00000312917.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA1	NM_001145716.2	c.-81+19626A>C		intron_variant			NP_001139188.1
PNPLA1	NM_173676.2	c.-81+19626A>C		intron_variant			NP_775947.2
PNPLA1	XM_011514520.3	c.-81+19626A>C		intron_variant			XP_011512822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA1	ENST00000312917.9	c.-81+19626A>C		intron_variant		1		ENSP00000321116
PNPLA1	ENST00000388715.7	c.-81+19626A>C		intron_variant		1		ENSP00000373367

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63870 AN: 152006 Hom.: 14060 Cov.: 33

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.420 AC: 63936 AN: 152124 Hom.: 14080 Cov.: 33 AF XY: 0.425 AC XY: 31609 AN XY: 74374

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.393

Alfa AF: 0.374 Hom.: 3031

Bravo AF: 0.420

Asia WGS AF: 0.448 AC: 1555 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.71

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: rs6903663; hg19: chr6-36230664;