Genetic Variant NM_000237.3:c.*2075T>G (chr8-19967385-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00300

Publications

15 publications found

Variant links:

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

LPL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.*2075T>G		downstream_gene	N/A	NP_000228.1	P06858

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LPL	ENST00000650287.1	MANE Select	c.*2075T>G	downstream_gene	N/A	ENSP00000497642.1	P06858
LPL	ENST00000965928.1		c.*2075T>G	downstream_gene	N/A	ENSP00000635987.1
LPL	ENST00000965929.1		c.*2075T>G	downstream_gene	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32220

AN:

152100

Hom.:

4253

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.212

AC:

32218

AN:

152220

Hom.:

4255

Cov.:

AF XY:

0.211

AC XY:

15728

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0643

AC:

2671

AN:

41554

American (AMR)

AF:

0.228

AC:

3488

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

1228

AN:

3472

East Asian (EAS)

AF:

0.186

AC:

965

AN:

5186

South Asian (SAS)

AF:

0.278

AC:

1340

AN:

4814

European-Finnish (FIN)

AF:

0.232

AC:

2455

AN:

10596

Middle Eastern (MID)

AF:

0.428

AC:

125

AN:

292

European-Non Finnish (NFE)

AF:

0.283

AC:

19233

AN:

68000

Other (OTH)

AF:

0.251

AC:

531

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1245

2490

3734

4979

6224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.263

Hom.:

8565

Bravo

AF:

0.205

Asia WGS

AF:

0.220

AC:

766

AN:

3472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.0

(source)

DANN

Benign

0.51

PhyloP100

0.0030

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over