8-19967385-T-G

Variant names:

• chr8-19967385-T-G
• rs9644636
• NM_000237.3:c.*2075T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000237.3(LPL):​c.*2075T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,220 control chromosomes in the GnomAD database, including 4,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (4255 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LPL NM_000237.3 downstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00300

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-19967385-T-G is Benign according to our data. Variant chr8-19967385-T-G is described in ClinVar as [Benign]. Clinvar id is 1181642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.*2075T>G		downstream_gene_variant		ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.*2075T>G		downstream_gene_variant			NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*2326T>G		downstream_gene_variant				ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32220 AN: 152100 Hom.: 4253 Cov.: 33

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.253

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.212 AC: 32218 AN: 152220 Hom.: 4255 Cov.: 33 AF XY: 0.211 AC XY: 15728 AN XY: 74424

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.251

Alfa AF: 0.270 Hom.: 7204

Bravo AF: 0.205

Asia WGS AF: 0.220 AC: 766 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 02, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9644636; hg19: chr8-19824896;