rs4922115

Variant names:

• chr8-19965319-G-A
• rs4922115
• NM_000237.3:c.*9G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-19965319-G-A
• chr8-19965319-G-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.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 779,480 control chromosomes in the GnomAD database, including 8,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1651 hom., cov: 32)
  • Exomes 𝑓: 0.15 (7222 hom.)
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0420
• Publications: 26 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-19965319-G-A is Benign according to our data. Variant chr8-19965319-G-A is described in ClinVar as Benign. ClinVar VariationId is 362417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 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.*9G>A		3_prime_UTR	Exon 10 of 10	NP_000228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.*9G>A		3_prime_UTR	Exon 10 of 10	ENSP00000497642.1
	LPL	ENST00000650478.1		n.*260G>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000497560.1
	LPL	ENST00000650478.1		n.*260G>A		3_prime_UTR	Exon 4 of 4	ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21918 AN: 152030 Hom.: 1648 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.146 AC: 36519 AN: 250584 AF XY: 0.147

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.0951

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.147 AC: 92435 AN: 627332 Hom.: 7222 Cov.: 0 AF XY: 0.148 AC XY: 50474 AN XY: 341746

African (AFR) AF: 0.113 AC: 2001 AN: 17632

American (AMR) AF: 0.146 AC: 6372 AN: 43620

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 4898 AN: 20914

East Asian (EAS) AF: 0.0762 AC: 2743 AN: 36016

South Asian (SAS) AF: 0.132 AC: 9168 AN: 69524

European-Finnish (FIN) AF: 0.155 AC: 8209 AN: 53016

Middle Eastern (MID) AF: 0.171 AC: 709 AN: 4146

European-Non Finnish (NFE) AF: 0.153 AC: 53288 AN: 349410

Other (OTH) AF: 0.153 AC: 5047 AN: 33054

GnomAD4 genome AF: 0.144 AC: 21928 AN: 152148 Hom.: 1651 Cov.: 32 AF XY: 0.144 AC XY: 10701 AN XY: 74382

African (AFR) AF: 0.114 AC: 4716 AN: 41504

American (AMR) AF: 0.156 AC: 2380 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3472

East Asian (EAS) AF: 0.0950 AC: 492 AN: 5178

South Asian (SAS) AF: 0.126 AC: 606 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1656 AN: 10584

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10710 AN: 67980

Other (OTH) AF: 0.145 AC: 307 AN: 2116

Alfa AF: 0.151 Hom.: 2582

Bravo AF: 0.143

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Dystrophin deficiency (1)
-	-	1	Hyperlipoproteinemia, type I (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4922115; hg19: chr8-19822830;