rs325

Positions:

• chr8-19961817-T-C
• chr8-19961817-T-G

Variant summary

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

The NM_000237.3(LPL):​c.1323-298T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,044 control chromosomes in the GnomAD database, including 611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.090 (611 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.164

Genes affected

LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-19961817-T-C is Benign according to our data. Variant chr8-19961817-T-C is described in ClinVar as [Benign]. Clinvar id is 1174434.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19961817-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPL	NM_000237.3	c.1323-298T>C		intron_variant		ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1323-298T>C		intron_variant			NM_000237.3	ENSP00000497642	P1
LPL	ENST00000650478.1	c.*146-298T>C		intron_variant, NMD_transcript_variant				ENSP00000497560

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13740 AN: 151926 Hom.: 612 Cov.: 32

Gnomad AFR AF: 0.0705

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0903 AC: 13727 AN: 152044 Hom.: 611 Cov.: 32 AF XY: 0.0898 AC XY: 6672 AN XY: 74336

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.0799

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0965

Gnomad4 FIN AF: 0.0909

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.0856 Hom.: 114

Bravo AF: 0.0882

Asia WGS AF: 0.100 AC: 346 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.75

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: rs325; hg19: chr8-19819328;