rs256

Positions:

• chr8-19954456-C-T

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.775+103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,154,498 control chromosomes in the GnomAD database, including 12,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1379 hom., cov: 33)
  • Exomes 𝑓: 0.15 (10828 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.529

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=-0.82).
• BP6: Variant 8-19954456-C-T is Benign according to our data. Variant chr8-19954456-C-T is described in ClinVar as [Benign]. Clinvar id is 1285932.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19954456-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.775+103C>T		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.775+103C>T		intron_variant			NM_000237.3	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18831 AN: 152110 Hom.: 1375 Cov.: 33

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.145 AC: 145604 AN: 1002270 Hom.: 10828 AF XY: 0.147 AC XY: 75054 AN XY: 510676

Gnomad4 AFR exome AF: 0.0596

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.124 AC: 18832 AN: 152228 Hom.: 1379 Cov.: 33 AF XY: 0.125 AC XY: 9320 AN XY: 74426

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.128

Alfa AF: 0.145 Hom.: 2664

Bravo AF: 0.122

Asia WGS AF: 0.197 AC: 683 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

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.92
DANN	Benign	0.48

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: rs256; hg19: chr8-19811967;