rs271

Variant names:

• chr8-19956191-G-A
• rs271
• NM_000237.3:c.1018+108G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-19956191-G-A
• chr8-19956191-G-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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.495
• Publications: 38 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=-0.9).
• BP6: Variant 8-19956191-G-A is Benign according to our data. Variant chr8-19956191-G-A is described in ClinVar as Benign. ClinVar VariationId is 1289075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1018+108G>A		intron_variant	Intron 6 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1018+108G>A		intron_variant	Intron 6 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.79+108G>A		intron_variant	Intron 1 of 3			ENSP00000497560.1

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

African (AFR) AF: 0.0589 AC: 1833 AN: 31142

American (AMR) AF: 0.148 AC: 6439 AN: 43426

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 4440 AN: 25268

East Asian (EAS) AF: 0.215 AC: 8383 AN: 38992

South Asian (SAS) AF: 0.163 AC: 13473 AN: 82518

European-Finnish (FIN) AF: 0.107 AC: 4603 AN: 43198

Middle Eastern (MID) AF: 0.136 AC: 584 AN: 4300

European-Non Finnish (NFE) AF: 0.146 AC: 147610 AN: 1012132

Other (OTH) AF: 0.143 AC: 8051 AN: 56498

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

African (AFR) AF: 0.0622 AC: 2584 AN: 41542

American (AMR) AF: 0.155 AC: 2374 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 609 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1139 AN: 5174

South Asian (SAS) AF: 0.163 AC: 789 AN: 4826

European-Finnish (FIN) AF: 0.103 AC: 1094 AN: 10604

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10176 AN: 67988

Other (OTH) AF: 0.133 AC: 281 AN: 2116

Alfa AF: 0.117 Hom.: 468

Bravo AF: 0.125

Asia WGS AF: 0.189 AC: 657 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

- -

Apr 01, 2019

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	-0.90
CADD	Benign	0.34
DANN	Benign	0.23
PhyloP100		-0.49

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

Other links and lift over

dbSNP: rs271; hg19: chr8-19813702; COSMIC: COSV60933459; COSMIC: COSV60933459;