rs3200218

Variant names:

• chr8-19966560-A-G
• rs3200218
• NM_000237.3:c.*1250A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-19966560-A-G
• chr8-19966560-A-T

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.*1250A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,200 control chromosomes in the GnomAD database, including 3,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3247 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.643
• Publications: 31 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=-0.79).
• BP6: Variant 8-19966560-A-G is Benign according to our data. Variant chr8-19966560-A-G is described in ClinVar as Benign. ClinVar VariationId is 362441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 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.*1250A>G		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.*1250A>G		3_prime_UTR	Exon 10 of 10	ENSP00000497642.1
	LPL	ENST00000650478.1		n.*1501A>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000497560.1
	LPL	ENST00000650478.1		n.*1501A>G		3_prime_UTR	Exon 4 of 4	ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29529 AN: 152080 Hom.: 3251 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.182

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.194 AC: 29527 AN: 152200 Hom.: 3247 Cov.: 32 AF XY: 0.194 AC XY: 14430 AN XY: 74400

African (AFR) AF: 0.118 AC: 4903 AN: 41546

American (AMR) AF: 0.184 AC: 2805 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3468

East Asian (EAS) AF: 0.130 AC: 676 AN: 5188

South Asian (SAS) AF: 0.146 AC: 702 AN: 4820

European-Finnish (FIN) AF: 0.305 AC: 3219 AN: 10568

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16144 AN: 68004

Other (OTH) AF: 0.180 AC: 381 AN: 2116

Alfa AF: 0.220 Hom.: 2035

Bravo AF: 0.184

Asia WGS AF: 0.112 AC: 392 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hyperlipoproteinemia, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.70
PhyloP100		0.64

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: rs3200218; hg19: chr8-19824071;