rs314

Positions:

• chr8-19960531-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000237.3(LPL):​c.1140-370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,962 control chromosomes in the GnomAD database, including 13,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.39 (13852 hom., cov: 31)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-19960531-G-A is Benign according to our data. Variant chr8-19960531-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPL	NM_000237.3	c.1140-370G>A		intron_variant		ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1140-370G>A		intron_variant			NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.80-370G>A		intron_variant				ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59095 AN: 151844 Hom.: 13814 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.361

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.389 AC: 59178 AN: 151962 Hom.: 13852 Cov.: 31 AF XY: 0.383 AC XY: 28486 AN XY: 74286

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.360

Alfa AF: 0.349 Hom.: 1440

Bravo AF: 0.403

Asia WGS AF: 0.289 AC: 1001 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs314; hg19: chr8-19818042;