10-88728358-T-C

Position:

• chr10-88728358-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPK	NM_001080518.2	c.223+1446T>C		intron_variant		ENST00000404190.3	NP_001073987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPK	ENST00000404190.3	c.223+1446T>C		intron_variant		1	NM_001080518.2	ENSP00000383900.1
KRT8P38	ENST00000441370.1	n.874T>C		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116921 AN: 152028 Hom.: 45799 Cov.: 33

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.: 0 AF XY: 0.740 AC XY: 16101 AN XY: 21756

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.834

Gnomad4 ASJ exome AF: 0.777

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.818

Gnomad4 FIN exome AF: 0.727

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.732

GnomAD4 genome AF: 0.769 AC: 117041 AN: 152146 Hom.: 45860 Cov.: 33 AF XY: 0.774 AC XY: 57516 AN XY: 74352

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.778

Alfa AF: 0.722 Hom.: 4996

Bravo AF: 0.781

Asia WGS AF: 0.920 AC: 3199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.9
DANN	Benign	0.27

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: rs416957; hg19: chr10-90488115; COSMIC: COSV68201984;