Genetic Variant NM_001080518.2:c.223+469C>T (chr10-88727381-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080518.2(LIPK):c.223+469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 184,084 control chromosomes in the GnomAD database, including 54,707 homozygotes. 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 0.78 ( 46973 hom., cov: 33)

Exomes 𝑓: 0.69 ( 7734 hom. )

Consequence

LIPK
NM_001080518.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

Publications

1 publications found

Variant links:

Genes affected

LIPK (HGNC:23444): (lipase family member K) Predicted to enable lipoprotein lipase activity. Predicted to be involved in cornification. Predicted to be located in extracellular region. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LIPK links:

KRT8P38 (HGNC:39872): (keratin 8 pseudogene 38)

KRT8P38 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080518.2. 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
	LIPK	NM_001080518.2	MANE Select	c.223+469C>T		intron	N/A	NP_001073987.1	Q5VXJ0
	LIPK	NM_001378091.1		c.223+469C>T		intron	N/A	NP_001365020.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPK	ENST00000404190.3	TSL:1 MANE Select	c.223+469C>T		intron	N/A	ENSP00000383900.1	Q5VXJ0
	KRT8P38	ENST00000441370.1	TSL:6	n.-104C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.777

AC:

118167

AN:

152100

Hom.:

46905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.931

Gnomad AMI

AF:

0.852

Gnomad AMR

AF:

0.800

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.820

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.783

GnomAD4 exome

AF:

0.685

AC:

21840

AN:

31866

Hom.:

7734

AF XY:

0.695

AC XY:

11177

AN XY:

16076

show subpopulations

African (AFR)

AF:

0.929

AC:

197

AN:

212

American (AMR)

AF:

0.815

AC:

1336

AN:

1640

Ashkenazi Jewish (ASJ)

AF:

0.748

AC:

477

AN:

638

East Asian (EAS)

AF:

0.998

AC:

577

AN:

578

South Asian (SAS)

AF:

0.795

AC:

2326

AN:

2926

European-Finnish (FIN)

AF:

0.684

AC:

1027

AN:

1502

Middle Eastern (MID)

AF:

0.792

AC:

114

AN:

144

European-Non Finnish (NFE)

AF:

0.646

AC:

14361

AN:

22246

Other (OTH)

AF:

0.720

AC:

1425

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

329

658

987

1316

1645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.777

AC:

118295

AN:

152218

Hom.:

46973

Cov.:

AF XY:

0.781

AC XY:

58124

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.932

AC:

38724

AN:

41564

American (AMR)

AF:

0.801

AC:

12249

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

2653

AN:

3470

East Asian (EAS)

AF:

0.996

AC:

5168

AN:

5188

South Asian (SAS)

AF:

0.820

AC:

3959

AN:

4826

European-Finnish (FIN)

AF:

0.710

AC:

7501

AN:

10566

Middle Eastern (MID)

AF:

0.806

AC:

237

AN:

294

European-Non Finnish (NFE)

AF:

0.667

AC:

45366

AN:

67988

Other (OTH)

AF:

0.786

AC:

1661

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1280

2559

3839

5118

6398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.726

Hom.:

9802

Bravo

AF:

0.792

Asia WGS

AF:

0.921

AC:

3204

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.5

(source)

DANN

Benign

0.21

PhyloP100

-0.010

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over