rs316

Variant names:

• chr8-19960925-C-A
• rs316
• NM_000237.3:c.1164C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-19960925-C-A
• chr8-19960925-C-G
• chr8-19960925-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000237.3(LPL):​c.1164C>A​(p.Thr388Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,340 control chromosomes in the GnomAD database, including 14,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2009 hom., cov: 31)
  • Exomes 𝑓: 0.13 (12298 hom.)
• Consequence: LPL NM_000237.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.57
• Publications: 100 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 8-19960925-C-A is Benign according to our data. Variant chr8-19960925-C-A is described in ClinVar as Benign. ClinVar VariationId is 362413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 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.1164C>A	p.Thr388Thr	synonymous	Exon 8 of 10	NP_000228.1	P06858

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.1164C>A	p.Thr388Thr	synonymous	Exon 8 of 10	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.1164C>A	p.Thr388Thr	synonymous	Exon 10 of 12	ENSP00000635987.1
	LPL	ENST00000965929.1		c.1161C>A	p.Thr387Thr	synonymous	Exon 8 of 10	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23541 AN: 151804 Hom.: 2000 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.110

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.135 AC: 33843 AN: 251348 AF XY: 0.133

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.0965

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.127 AC: 185694 AN: 1460422 Hom.: 12298 Cov.: 33 AF XY: 0.127 AC XY: 92390 AN XY: 726602

African (AFR) AF: 0.226 AC: 7539 AN: 33432

American (AMR) AF: 0.133 AC: 5943 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 5481 AN: 26106

East Asian (EAS) AF: 0.0777 AC: 3084 AN: 39684

South Asian (SAS) AF: 0.127 AC: 10988 AN: 86224

European-Finnish (FIN) AF: 0.134 AC: 7166 AN: 53396

Middle Eastern (MID) AF: 0.125 AC: 712 AN: 5712

European-Non Finnish (NFE) AF: 0.123 AC: 136657 AN: 1110800

Other (OTH) AF: 0.135 AC: 8124 AN: 60352

GnomAD4 genome AF: 0.155 AC: 23575 AN: 151918 Hom.: 2009 Cov.: 31 AF XY: 0.154 AC XY: 11435 AN XY: 74254

African (AFR) AF: 0.223 AC: 9225 AN: 41416

American (AMR) AF: 0.141 AC: 2152 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 696 AN: 3472

East Asian (EAS) AF: 0.0964 AC: 494 AN: 5126

South Asian (SAS) AF: 0.122 AC: 587 AN: 4810

European-Finnish (FIN) AF: 0.130 AC: 1367 AN: 10546

Middle Eastern (MID) AF: 0.115 AC: 33 AN: 286

European-Non Finnish (NFE) AF: 0.127 AC: 8604 AN: 67956

Other (OTH) AF: 0.144 AC: 305 AN: 2112

Alfa AF: 0.133 Hom.: 4443

Bravo AF: 0.157

Asia WGS AF: 0.128 AC: 442 AN: 3478

EpiCase AF: 0.122

EpiControl AF: 0.121

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Hyperlipoproteinemia, type I (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		-2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs316; hg19: chr8-19818436; COSMIC: COSV108136730;