8-19961566-T-G

Position:

• chr8-19961566-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.1322+483T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,060 control chromosomes in the GnomAD database, including 6,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6080 hom., cov: 31)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.172

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=-0.6).
• BP6: Variant 8-19961566-T-G is Benign according to our data. Variant chr8-19961566-T-G is described in ClinVar as [Benign]. Clinvar id is 1165812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19961566-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPL	NM_000237.3	c.1322+483T>G		intron_variant		ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1322+483T>G		intron_variant			NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*145+483T>G		intron_variant				ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42808 AN: 151942 Hom.: 6073 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.282 AC: 42827 AN: 152060 Hom.: 6080 Cov.: 31 AF XY: 0.278 AC XY: 20682 AN XY: 74340

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.273

Alfa AF: 0.203 Hom.: 629

Bravo AF: 0.284

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.78

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: rs320; hg19: chr8-19819077;