rs255

Variant names:

• chr8-19954390-T-C
• rs255
• NM_000237.3:c.775+37T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-19954390-T-C
• chr8-19954390-T-A

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.775+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,581,682 control chromosomes in the GnomAD database, including 20,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2545 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17824 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0960
• Publications: 28 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, 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=-0.83).
• BP6: Variant 8-19954390-T-C is Benign according to our data. Variant chr8-19954390-T-C is described in ClinVar as Benign. ClinVar VariationId is 1182670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 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.775+37T>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.775+37T>C		intron	N/A	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.775+37T>C		intron	N/A	ENSP00000635987.1
	LPL	ENST00000965929.1		c.772+37T>C		intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26799 AN: 152036 Hom.: 2533 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.167 AC: 41243 AN: 247204 AF XY: 0.168

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.224

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.155 AC: 221787 AN: 1429528 Hom.: 17824 Cov.: 26 AF XY: 0.157 AC XY: 112071 AN XY: 713296

African (AFR) AF: 0.230 AC: 7548 AN: 32818

American (AMR) AF: 0.160 AC: 7128 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 5041 AN: 25922

East Asian (EAS) AF: 0.217 AC: 8591 AN: 39504

South Asian (SAS) AF: 0.219 AC: 18676 AN: 85448

European-Finnish (FIN) AF: 0.105 AC: 5584 AN: 53340

Middle Eastern (MID) AF: 0.137 AC: 785 AN: 5716

European-Non Finnish (NFE) AF: 0.147 AC: 158955 AN: 1083006

Other (OTH) AF: 0.160 AC: 9479 AN: 59306

GnomAD4 genome AF: 0.176 AC: 26835 AN: 152154 Hom.: 2545 Cov.: 33 AF XY: 0.176 AC XY: 13104 AN XY: 74396

African (AFR) AF: 0.226 AC: 9375 AN: 41480

American (AMR) AF: 0.174 AC: 2663 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1150 AN: 5172

South Asian (SAS) AF: 0.224 AC: 1082 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1092 AN: 10606

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10232 AN: 68000

Other (OTH) AF: 0.168 AC: 356 AN: 2116

Alfa AF: 0.169 Hom.: 739

Bravo AF: 0.181

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

ClinVar submissions

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	-0.83
CADD	Benign	4.8
DANN	Benign	0.27
PhyloP100		-0.096

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: rs255; hg19: chr8-19811901; COSMIC: COSV60929933; COSMIC: COSV60929933;