rs271

chr8-19956191-G-Achr8-19956191-G-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.1018+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,489,690 control chromosomes in the GnomAD database, including 16,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1427 hom., cov: 32)
  • Exomes 𝑓: 0.15 (14719 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.495

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=-0.9).
• BP6: Variant 8-19956191-G-A is Benign according to our data. Variant chr8-19956191-G-A is described in ClinVar as [Benign]. Clinvar id is 1289075.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19956191-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.1018+108G>A		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.1018+108G>A		intron_variant			NM_000237.3	P1
LPL	ENST00000650478.1	c.79+108G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19272 AN: 152096 Hom.: 1424 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.146 AC: 195416 AN: 1337474 Hom.: 14719 AF XY: 0.147 AC XY: 98876 AN XY: 670868

Gnomad4 AFR exome AF: 0.0589

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.127 AC: 19272 AN: 152216 Hom.: 1427 Cov.: 32 AF XY: 0.128 AC XY: 9500 AN XY: 74436

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0859 Hom.: 161

Bravo AF: 0.125

Asia WGS AF: 0.189 AC: 657 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

Apr 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.34
Dann	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs271; hg19: chr8-19813702; COSMIC: COSV60933459; COSMIC: COSV60933459;