rs3208305

Variant names:

• chr8-19966137-A-T
• rs3208305
• NM_000237.3:c.*827A>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.*827A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,874 control chromosomes in the GnomAD database, including 10,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10561 hom., cov: 31)
  • 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: -0.282
• Publications: 30 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=-0.92).
• BP6: Variant 8-19966137-A-T is Benign according to our data. Variant chr8-19966137-A-T is described in ClinVar as Benign. ClinVar VariationId is 362430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 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.*827A>T		3_prime_UTR	Exon 10 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.*827A>T		3_prime_UTR	Exon 10 of 10	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.*827A>T		3_prime_UTR	Exon 12 of 12	ENSP00000635987.1
	LPL	ENST00000965929.1		c.*827A>T		3_prime_UTR	Exon 10 of 10	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53831 AN: 151758 Hom.: 10544 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.337

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 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) AC: 0 AN: 0

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: 0.355 AC: 53890 AN: 151874 Hom.: 10561 Cov.: 31 AF XY: 0.350 AC XY: 25963 AN XY: 74200

African (AFR) AF: 0.525 AC: 21727 AN: 41402

American (AMR) AF: 0.299 AC: 4565 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3466

East Asian (EAS) AF: 0.203 AC: 1052 AN: 5174

South Asian (SAS) AF: 0.246 AC: 1188 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2724 AN: 10504

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19912 AN: 67952

Other (OTH) AF: 0.337 AC: 708 AN: 2100

Alfa AF: 0.324 Hom.: 1150

Bravo AF: 0.365

Asia WGS AF: 0.254 AC: 883 AN: 3472

ClinVar

ClinVar submissions

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	-0.92
CADD	Benign	0.79
DANN	Benign	0.45
PhyloP100		-0.28

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: rs3208305; hg19: chr8-19823648;