10-88727381-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPK	NM_001080518.2	c.223+469C>T		intron_variant	Intron 3 of 9	ENST00000404190.3	NP_001073987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPK	ENST00000404190.3	c.223+469C>T		intron_variant	Intron 3 of 9	1	NM_001080518.2	ENSP00000383900.1
KRT8P38	ENST00000441370.1	n.-104C>T		upstream_gene_variant		6

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

Gnomad4 AFR exome AF: 0.929

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.748

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.684

Gnomad4 NFE exome AF: 0.646

Gnomad4 OTH exome AF: 0.720

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

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.786

Alfa AF: 0.722 Hom.: 9457

Bravo AF: 0.792

Asia WGS AF: 0.921 AC: 3204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.21

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

LitVar

Other links and lift over

dbSNP: rs378308; hg19: chr10-90487138;