10-88728358-T-C

Variant names:

• chr10-88728358-T-C
• rs416957
• NM_001080518.2:c.223+1446T>C

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+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
• Publications: 0 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=-0.61).
• 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 rank	MANE	Protein	UniProt
LIPK	NM_001080518.2	c.223+1446T>C		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+1446T>C		intron_variant	Intron 3 of 9	1	NM_001080518.2	ENSP00000383900.1
KRT8P38	ENST00000441370.1	n.874T>C		non_coding_transcript_exon_variant	Exon 1 of 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

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

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

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.9
DANN	Benign	0.27
PhyloP100		-0.32
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: rs416957; hg19: chr10-90488115; COSMIC: COSV68201984;