15-89677777-T-G

Variant summary

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

The NM_002666.5(PLIN1):c.-14-274A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 425,028 control chromosomes in the GnomAD database, including 162,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.88 (58101 hom., cov: 21)
  • Exomes 𝑓: 0.85 (104838 hom.)
• Consequence: PLIN1 NM_002666.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.679

Genes affected

PLIN1 (HGNC:9076): (perilipin 1) The protein encoded by this gene coats lipid storage droplets in adipocytes, thereby protecting them until they can be broken down by hormone-sensitive lipase. The encoded protein is the major cAMP-dependent protein kinase substrate in adipocytes and, when unphosphorylated, may play a role in the inhibition of lipolysis. Alternatively spliced transcript variants varying in the 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Feb 2009]

PEX11A (HGNC:8852): (peroxisomal biogenesis factor 11 alpha) This gene is a member of the PEX11 family, which is composed of membrane elongation factors involved in regulation of peroxisome maintenance and proliferation. This gene product interacts with peroxisomal membrane protein 19 and may respond to outside stimuli to increase peroxisome abundance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 15-89677777-T-G is Benign according to our data. Variant chr15-89677777-T-G is described in ClinVar as [Benign]. Clinvar id is 1178857.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5	c.-14-274A>C		intron_variant		ENST00000300055.10
PLIN1	NM_001145311.2	c.-14-274A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN1	ENST00000300055.10	c.-14-274A>C		intron_variant		1	NM_002666.5	P1
PLIN1	ENST00000531697.1	n.97-274A>C		intron_variant, non_coding_transcript_variant		1
PLIN1	ENST00000430628.2	c.-14-274A>C		intron_variant		5		P1
PEX11A	ENST00000557982.1	n.633A>C		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.879 AC: 128968 AN: 146692 Hom.: 58067 Cov.: 21

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.958

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.850 AC: 236413 AN: 278258 Hom.: 104838 Cov.: 0 AF XY: 0.844 AC XY: 123527 AN XY: 146304

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.948

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.739

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.931

Gnomad4 OTH exome AF: 0.866

GnomAD4 genome AF: 0.879 AC: 129035 AN: 146770 Hom.: 58101 Cov.: 21 AF XY: 0.866 AC XY: 61774 AN XY: 71310

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.878

Alfa AF: 0.910 Hom.: 6013

Bravo AF: 0.871

Asia WGS AF: 0.512 AC: 1773 AN: 3456

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.80
Dann	Benign	0.64

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: rs12906281; hg19: chr15-90221008;