NM_001080518.2:c.223+469C>T

Variant names:

• chr10-88727381-C-T
• rs378308
• NM_001080518.2:c.223+469C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 1 publications found

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]

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

ACMG classification

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

Selected	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
	LIPK	NM_001378091.1		c.223+469C>T		intron	N/A	NP_001365020.1

Ensembl Transcripts

Selected	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
	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.: 33

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

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

GnomAD4 genome AF: 0.777 AC: 118295 AN: 152218 Hom.: 46973 Cov.: 33 AF XY: 0.781 AC XY: 58124 AN XY: 74410

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

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
DANN	Benign	0.21
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs378308; hg19: chr10-90487138;