8-19966981-T-C

Variant names:

• chr8-19966981-T-C
• rs13702
• NM_000237.3:c.*1671T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000237.3(LPL):​c.*1671T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,466 control chromosomes in the GnomAD database, including 10,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10304 hom., cov: 33)
  • Exomes 𝑓: 0.27 (21 hom.)
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -1.17

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-19966981-T-C is Benign according to our data. Variant chr8-19966981-T-C is described in ClinVar as [Benign]. Clinvar id is 40131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.*1671T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.*1671T>C		3_prime_UTR_variant	Exon 10 of 10		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*1922T>C		non_coding_transcript_exon_variant	Exon 4 of 4			ENSP00000497560.1
LPL	ENST00000650478.1	n.*1922T>C		3_prime_UTR_variant	Exon 4 of 4			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53381 AN: 151912 Hom.: 10288 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.273 AC: 119 AN: 436 Hom.: 21 Cov.: 0 AF XY: 0.252 AC XY: 66 AN XY: 262

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.352 AC: 53441 AN: 152030 Hom.: 10304 Cov.: 33 AF XY: 0.347 AC XY: 25766 AN XY: 74302

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.332

Alfa AF: 0.306 Hom.: 13237

Bravo AF: 0.361

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24990426, 21386085, 25814643, 26820803, 23246289) -

Hyperlipoproteinemia, type I Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

High density lipoprotein cholesterol level quantitative trait locus 11 Other:1

Jan 10, 2013

OMIM

Significance: association

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.65

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: rs13702; hg19: chr8-19824492; COSMIC: COSV60931277;