15-89667816-A-T

Variant names:

• chr15-89667816-A-T
• rs894162
• NM_002666.5:c.772-23T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002666.5(PLIN1):​c.772-23T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,546,456 control chromosomes in the GnomAD database, including 736,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68524 hom., cov: 34)
  • Exomes 𝑓: 0.98 (668163 hom.)
• Consequence: PLIN1 NM_002666.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.01
• Publications: 5 publications found

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]

PLIN1 Gene-Disease associations (from GenCC):

• PLIN1-related familial partial lipodystrophy

  Inheritance: AD Classification: STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 15-89667816-A-T is Benign according to our data. Variant chr15-89667816-A-T is described in ClinVar as Benign. ClinVar VariationId is 1250333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5	c.772-23T>A		intron_variant	Intron 6 of 8	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2	c.772-23T>A		intron_variant	Intron 6 of 8		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10	c.772-23T>A		intron_variant	Intron 6 of 8	1	NM_002666.5	ENSP00000300055.5
PLIN1	ENST00000430628.2	c.772-23T>A		intron_variant	Intron 6 of 8	5		ENSP00000402167.2
PLIN1	ENST00000560330.1	c.-176T>A		upstream_gene_variant		5		ENSP00000453426.1

Frequencies

GnomAD3 genomes AF: 0.946 AC: 144041 AN: 152190 Hom.: 68488 Cov.: 34

Gnomad AFR AF: 0.922

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.941

GnomAD2 exomes AF: 0.923 AC: 139202 AN: 150790 AF XY: 0.932

Gnomad AFR exome AF: 0.920

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.995

Gnomad EAS exome AF: 0.732

Gnomad FIN exome AF: 0.952

Gnomad NFE exome AF: 0.997

Gnomad OTH exome AF: 0.944

GnomAD4 exome AF: 0.977 AC: 1362369 AN: 1394148 Hom.: 668163 Cov.: 48 AF XY: 0.977 AC XY: 672255 AN XY: 687938

African (AFR) AF: 0.918 AC: 29179 AN: 31790

American (AMR) AF: 0.784 AC: 28013 AN: 35714

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 25022 AN: 25166

East Asian (EAS) AF: 0.713 AC: 25689 AN: 36030

South Asian (SAS) AF: 0.951 AC: 75405 AN: 79304

European-Finnish (FIN) AF: 0.953 AC: 41173 AN: 43210

Middle Eastern (MID) AF: 0.981 AC: 5580 AN: 5690

European-Non Finnish (NFE) AF: 0.997 AC: 1076361 AN: 1079256

Other (OTH) AF: 0.965 AC: 55947 AN: 57988

GnomAD4 genome AF: 0.946 AC: 144134 AN: 152308 Hom.: 68524 Cov.: 34 AF XY: 0.941 AC XY: 70081 AN XY: 74466

African (AFR) AF: 0.922 AC: 38316 AN: 41556

American (AMR) AF: 0.845 AC: 12936 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3454 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3809 AN: 5166

South Asian (SAS) AF: 0.942 AC: 4549 AN: 4830

European-Finnish (FIN) AF: 0.951 AC: 10099 AN: 10620

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67797 AN: 68034

Other (OTH) AF: 0.936 AC: 1980 AN: 2116

Alfa AF: 0.977 Hom.: 13334

Bravo AF: 0.933

Asia WGS AF: 0.834 AC: 2901 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PLIN1-related familial partial lipodystrophy Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0030
DANN	Benign	0.76
PhyloP100		-4.0
PromoterAI		0.0048	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs894162; hg19: chr15-90211047; COSMIC: COSV55583966; COSMIC: COSV55583966;