rs7002728

Variant names:

• chr8-19951226-G-A
• rs7002728
• NM_000237.3:c.250-543G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-19951226-G-A
• chr8-19951226-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_000237.3(LPL):​c.250-543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00095 (0 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000953 (145/152224) while in subpopulation AFR AF= 0.00335 (139/41526). AF 95% confidence interval is 0.00289. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.250-543G>A		intron_variant	Intron 2 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.250-543G>A		intron_variant	Intron 2 of 9		NM_000237.3	ENSP00000497642.1

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 145 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.000953 AC: 145 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.000914 AC XY: 68 AN XY: 74426

Gnomad4 AFR AF: 0.00335

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.1
DANN	Benign	0.52

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: rs7002728; hg19: chr8-19808737;