rs4713951

Positions:

• chr6-36295214-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001374623.1(PNPLA1):​c.715-150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 722,284 control chromosomes in the GnomAD database, including 73,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14491 hom., cov: 32)
  • Exomes 𝑓: 0.45 (59325 hom.)
• Consequence: PNPLA1 NM_001374623.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-36295214-C-T is Benign according to our data. Variant chr6-36295214-C-T is described in ClinVar as [Benign]. Clinvar id is 1249564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA1	NM_001374623.1	c.715-150C>T		intron_variant		ENST00000636260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA1	ENST00000636260.2	c.715-150C>T		intron_variant		5	NM_001374623.1	A2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65387 AN: 151962 Hom.: 14469 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.447 AC: 254670 AN: 570204 Hom.: 59325 AF XY: 0.445 AC XY: 133858 AN XY: 301034

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.488

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.430 AC: 65445 AN: 152080 Hom.: 14491 Cov.: 32 AF XY: 0.438 AC XY: 32551 AN XY: 74328

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.404

Alfa AF: 0.428 Hom.: 21138

Bravo AF: 0.430

Asia WGS AF: 0.465 AC: 1616 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.032
DANN	Benign	0.76

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: rs4713951; hg19: chr6-36262991;