8-19942034-G-C

Variant names:

• chr8-19942034-G-C
• rs17410577
• NM_000237.3:c.88+2506G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000237.3(LPL):​c.88+2506G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,148 control chromosomes in the GnomAD database, including 2,386 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2386 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.88+2506G>C		intron	N/A	NP_000228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.88+2506G>C		intron	N/A	ENSP00000497642.1
	LPL	ENST00000965928.1		c.88+2506G>C		intron	N/A	ENSP00000635987.1
	LPL	ENST00000965929.1		c.88+2506G>C		intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25165 AN: 152030 Hom.: 2385 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 25167 AN: 152148 Hom.: 2386 Cov.: 32 AF XY: 0.166 AC XY: 12353 AN XY: 74374

African (AFR) AF: 0.123 AC: 5091 AN: 41530

American (AMR) AF: 0.163 AC: 2496 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 460 AN: 3464

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5184

South Asian (SAS) AF: 0.0864 AC: 417 AN: 4826

European-Finnish (FIN) AF: 0.268 AC: 2827 AN: 10558

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13332 AN: 67988

Other (OTH) AF: 0.154 AC: 324 AN: 2108

Alfa AF: 0.176 Hom.: 311

Bravo AF: 0.155

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.7
DANN	Benign	0.73
PhyloP100		-0.20

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: rs17410577; hg19: chr8-19799545;