rs10283151

Variant names:

• chr8-19965183-T-C
• rs10283151
• NM_000237.3:c.1428-127T>C

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.1428-127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 708,350 control chromosomes in the GnomAD database, including 521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (356 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (165 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.460
• Publications: 6 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: Genomics England PanelApp, Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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 8-19965183-T-C is Benign according to our data. Variant chr8-19965183-T-C is described in ClinVar as Benign. ClinVar VariationId is 1275704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.1428-127T>C		intron	N/A	NP_000228.1	P06858

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.1428-127T>C		intron	N/A	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.1428-127T>C		intron	N/A	ENSP00000635987.1
	LPL	ENST00000965929.1		c.1425-127T>C		intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5706 AN: 152182 Hom.: 355 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0310

GnomAD4 exome AF: 0.00644 AC: 3582 AN: 556050 Hom.: 165 AF XY: 0.00534 AC XY: 1601 AN XY: 299782

African (AFR) AF: 0.127 AC: 1967 AN: 15494

American (AMR) AF: 0.00830 AC: 294 AN: 35414

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 614 AN: 17220

East Asian (EAS) AF: 0.00 AC: 0 AN: 33860

South Asian (SAS) AF: 0.000366 AC: 21 AN: 57366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48996

Middle Eastern (MID) AF: 0.0200 AC: 77 AN: 3858

European-Non Finnish (NFE) AF: 0.000625 AC: 196 AN: 313654

Other (OTH) AF: 0.0137 AC: 413 AN: 30188

GnomAD4 genome AF: 0.0375 AC: 5716 AN: 152300 Hom.: 356 Cov.: 32 AF XY: 0.0353 AC XY: 2628 AN XY: 74488

African (AFR) AF: 0.128 AC: 5302 AN: 41540

American (AMR) AF: 0.0120 AC: 183 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000764 AC: 52 AN: 68030

Other (OTH) AF: 0.0307 AC: 65 AN: 2116

Alfa AF: 0.0296 Hom.: 47

Bravo AF: 0.0430

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.68
PhyloP100		-0.46

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: rs10283151; hg19: chr8-19822694;