rs412927

Variant names:

• chr10-88727523-A-G
• rs412927
• NM_001080518.2:c.223+611A>G

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+611A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 158,952 control chromosomes in the GnomAD database, including 48,639 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 (46894 hom., cov: 31)
  • Exomes 𝑓: 0.70 (1745 hom.)
• Consequence: LIPK NM_001080518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• 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=-0.9).
• 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+611A>G		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+611A>G		intron_variant	Intron 3 of 9	1	NM_001080518.2	ENSP00000383900.1
KRT8P38	ENST00000441370.1	n.39A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118010 AN: 151928 Hom.: 46827 Cov.: 31

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: 0.699 AC: 4824 AN: 6906 Hom.: 1745 Cov.: 0 AF XY: 0.698 AC XY: 2615 AN XY: 3744

African (AFR) AF: 0.931 AC: 54 AN: 58

American (AMR) AF: 0.827 AC: 311 AN: 376

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 63 AN: 88

East Asian (EAS) AF: 1.00 AC: 94 AN: 94

South Asian (SAS) AF: 0.882 AC: 455 AN: 516

European-Finnish (FIN) AF: 0.712 AC: 477 AN: 670

Middle Eastern (MID) AF: 0.625 AC: 15 AN: 24

European-Non Finnish (NFE) AF: 0.654 AC: 3049 AN: 4664

Other (OTH) AF: 0.736 AC: 306 AN: 416

GnomAD4 genome AF: 0.777 AC: 118137 AN: 152046 Hom.: 46894 Cov.: 31 AF XY: 0.781 AC XY: 58016 AN XY: 74292

African (AFR) AF: 0.931 AC: 38631 AN: 41494

American (AMR) AF: 0.801 AC: 12241 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2655 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5164 AN: 5184

South Asian (SAS) AF: 0.821 AC: 3942 AN: 4804

European-Finnish (FIN) AF: 0.710 AC: 7476 AN: 10536

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45353 AN: 67952

Other (OTH) AF: 0.786 AC: 1661 AN: 2114

Alfa AF: 0.758 Hom.: 6572

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	-0.90
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs412927; hg19: chr10-90487280;