Variant chr6-36301826-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001374623.1(PNPLA1):c.776-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,587,868 control chromosomes in the GnomAD database, including 133,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9962 hom., cov: 32)

Exomes 𝑓: 0.41 ( 123528 hom. )

Consequence

PNPLA1
NM_001374623.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.134

Variant links:

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]

PNPLA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-36301826-G-A is Benign according to our data. Variant chr6-36301826-G-A is described in ClinVar as [Benign]. Clinvar id is 1287688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA1	NM_001374623.1 linkuse as main transcript	c.776-35G>A		intron_variant		ENST00000636260.2	NP_001361552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA1	ENST00000636260.2 linkuse as main transcript	c.776-35G>A		intron_variant		5	NM_001374623.1	ENSP00000490785	A2

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49839

AN:

151982

Hom.:

9951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0994

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.391

AC:

92836

AN:

237148

Hom.:

20019

AF XY:

0.388

AC XY:

49532

AN XY:

127770

show subpopulations

Gnomad AFR exome

AF:

0.0889

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.264

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.407

AC:

584563

AN:

1435766

Hom.:

123528

Cov.:

AF XY:

0.403

AC XY:

286330

AN XY:

710544

show subpopulations

Gnomad4 AFR exome

AF:

0.0819

Gnomad4 AMR exome

AF:

0.536

Gnomad4 ASJ exome

AF:

0.374

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.449

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.328

AC:

49859

AN:

152102

Hom.:

9962

Cov.:

AF XY:

0.331

AC XY:

24590

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0994

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.365

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.394

Hom.:

23063

Bravo

AF:

0.315

Asia WGS

AF:

0.228

AC:

794

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Autosomal recessive congenital ichthyosis 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.1

DANN

Benign

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over