rs343

Variant names:

• chr8-19953276-C-A
• rs343
• NM_000237.3:c.430-34C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-19953276-C-A
• chr8-19953276-C-T

Variant summary

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

The NM_000237.3(LPL):​c.430-34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 1,316,296 control chromosomes in the GnomAD database, including 5,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (614 hom., cov: 33)
  • Exomes 𝑓: 0.090 (5058 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.510
• Publications: 22 publications found

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]

LPL Gene-Disease associations (from GenCC):

• familial lipoprotein lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperlipidemia, familial combined, LPL related

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-19953276-C-A is Benign according to our data. Variant chr8-19953276-C-A is described in ClinVar as [Benign]. Clinvar id is 1230139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.430-34C>A		intron_variant	Intron 3 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.430-34C>A		intron_variant	Intron 3 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000520959.5	c.202-34C>A		intron_variant	Intron 3 of 4	4		ENSP00000428496.1

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12729 AN: 152086 Hom.: 611 Cov.: 33

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0952

GnomAD2 exomes AF: 0.0984 AC: 24640 AN: 250484 AF XY: 0.0999

Gnomad AFR exome AF: 0.0498

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.0649

Gnomad NFE exome AF: 0.0813

Gnomad OTH exome AF: 0.0987

GnomAD4 exome AF: 0.0903 AC: 105163 AN: 1164092 Hom.: 5058 Cov.: 16 AF XY: 0.0924 AC XY: 54806 AN XY: 593430

African (AFR) AF: 0.0496 AC: 1378 AN: 27806

American (AMR) AF: 0.128 AC: 5676 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3349 AN: 24288

East Asian (EAS) AF: 0.137 AC: 5235 AN: 38234

South Asian (SAS) AF: 0.131 AC: 10527 AN: 80410

European-Finnish (FIN) AF: 0.0635 AC: 3373 AN: 53122

Middle Eastern (MID) AF: 0.0974 AC: 507 AN: 5204

European-Non Finnish (NFE) AF: 0.0838 AC: 70439 AN: 840538

Other (OTH) AF: 0.0931 AC: 4679 AN: 50264

GnomAD4 genome AF: 0.0837 AC: 12733 AN: 152204 Hom.: 614 Cov.: 33 AF XY: 0.0859 AC XY: 6392 AN XY: 74426

African (AFR) AF: 0.0514 AC: 2134 AN: 41514

American (AMR) AF: 0.130 AC: 1994 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3472

East Asian (EAS) AF: 0.155 AC: 803 AN: 5184

South Asian (SAS) AF: 0.126 AC: 606 AN: 4826

European-Finnish (FIN) AF: 0.0676 AC: 717 AN: 10602

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0824 AC: 5606 AN: 68008

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.0903 Hom.: 777

Bravo AF: 0.0861

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Sep 29, 2018

GeneDx

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	-0.87
CADD	Benign	0.49
DANN	Benign	0.17
PhyloP100		-0.51

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

Other links and lift over

dbSNP: rs343; hg19: chr8-19810787; COSMIC: COSV60930528; COSMIC: COSV60930528;