NM_000237.3:c.*371T>C

Variant names:

• chr8-19965681-T-C
• rs3289
• NM_000237.3:c.*371T>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.*371T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 197,868 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (173 hom., cov: 32)
  • Exomes 𝑓: 0.026 (31 hom.)
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.06
• Publications: 34 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=-0.72).
• BP6: Variant 8-19965681-T-C is Benign according to our data. Variant chr8-19965681-T-C is described in ClinVar as Benign. ClinVar VariationId is 362422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 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.*371T>C		3_prime_UTR	Exon 10 of 10	NP_000228.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.*371T>C		3_prime_UTR	Exon 10 of 10	ENSP00000497642.1
	LPL	ENST00000965928.1		c.*371T>C		3_prime_UTR	Exon 12 of 12	ENSP00000635987.1
	LPL	ENST00000965929.1		c.*371T>C		3_prime_UTR	Exon 10 of 10	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6012 AN: 152152 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0743

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0397

GnomAD4 exome AF: 0.0260 AC: 1185 AN: 45598 Hom.: 31 Cov.: 0 AF XY: 0.0258 AC XY: 595 AN XY: 23084

African (AFR) AF: 0.0730 AC: 124 AN: 1698

American (AMR) AF: 0.0243 AC: 54 AN: 2220

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 21 AN: 1728

East Asian (EAS) AF: 0.00146 AC: 5 AN: 3428

South Asian (SAS) AF: 0.0323 AC: 50 AN: 1546

European-Finnish (FIN) AF: 0.0190 AC: 40 AN: 2104

Middle Eastern (MID) AF: 0.0171 AC: 4 AN: 234

European-Non Finnish (NFE) AF: 0.0273 AC: 809 AN: 29604

Other (OTH) AF: 0.0257 AC: 78 AN: 3036

GnomAD4 genome AF: 0.0395 AC: 6013 AN: 152270 Hom.: 173 Cov.: 32 AF XY: 0.0385 AC XY: 2870 AN XY: 74450

African (AFR) AF: 0.0741 AC: 3079 AN: 41548

American (AMR) AF: 0.0349 AC: 534 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0417 AC: 201 AN: 4818

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0271 AC: 1846 AN: 68024

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0349 Hom.: 36

Bravo AF: 0.0410

Asia WGS AF: 0.0290 AC: 101 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	Hyperlipoproteinemia, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		1.1

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: rs3289; hg19: chr8-19823192;