Genetic Variant LIPK:c.223+1446T>C (chr10-88728358-T-C) – 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+1446T>C 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 192,720 control chromosomes in the GnomAD database, including 56,953 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 0.77 ( 45860 hom., cov: 33)

Exomes 𝑓: 0.73 ( 11093 hom. )

Consequence

LIPK
NM_001080518.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.323

Publications

0 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:

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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=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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+1446T>C		intron	N/A	NP_001073987.1	Q5VXJ0
	LIPK	NM_001378091.1		c.223+1446T>C		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+1446T>C		intron	N/A	ENSP00000383900.1	Q5VXJ0
	KRT8P38	ENST00000441370.1	TSL:6	n.874T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.769

AC:

116921

AN:

152028

Hom.:

45799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.852

Gnomad AMR

AF:

0.796

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.819

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.776

GnomAD4 exome

AF:

0.731

AC:

29642

AN:

40574

Hom.:

11093

Cov.:

AF XY:

0.740

AC XY:

16101

AN XY:

21756

show subpopulations

African (AFR)

AF:

0.895

AC:

696

AN:

778

American (AMR)

AF:

0.834

AC:

1602

AN:

1922

Ashkenazi Jewish (ASJ)

AF:

0.777

AC:

765

AN:

984

East Asian (EAS)

AF:

0.997

AC:

730

AN:

732

South Asian (SAS)

AF:

0.818

AC:

5862

AN:

7170

European-Finnish (FIN)

AF:

0.727

AC:

1404

AN:

1932

Middle Eastern (MID)

AF:

0.825

AC:

160

AN:

194

European-Non Finnish (NFE)

AF:

0.682

AC:

16740

AN:

24562

Other (OTH)

AF:

0.732

AC:

1683

AN:

2300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

361

723

1084

1446

1807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.769

AC:

117041

AN:

152146

Hom.:

45860

Cov.:

AF XY:

0.774

AC XY:

57516

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.906

AC:

37656

AN:

41554

American (AMR)

AF:

0.796

AC:

12181

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.753

AC:

2611

AN:

3468

East Asian (EAS)

AF:

0.996

AC:

5123

AN:

5142

South Asian (SAS)

AF:

0.820

AC:

3952

AN:

4822

European-Finnish (FIN)

AF:

0.710

AC:

7513

AN:

10578

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.667

AC:

45350

AN:

67964

Other (OTH)

AF:

0.778

AC:

1643

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1378

2757

4135

5514

6892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

850

1700

2550

3400

4250

<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:

0.730

Hom.:

5332

Bravo

AF:

0.781

Asia WGS

AF:

0.920

AC:

3199

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.9

(source)

DANN

Benign

0.27

PhyloP100

-0.32

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