17-28085798-T-C

Variant names:

• chr17-28085798-T-C
• rs4420579
• NM_016231.5:c.459-36805T>C

Variant summary

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

The NM_016231.5(NLK):​c.459-36805T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0608 in 152,158 control chromosomes in the GnomAD database, including 361 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 0.061 (361 hom., cov: 32)
• Consequence: NLK NM_016231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780
• Publications: 12 publications found

Genes affected

NLK (HGNC:29858): (nemo like kinase) Enables ubiquitin protein ligase binding activity. Involved in protein stabilization and transforming growth factor beta receptor signaling pathway. Predicted to be located in cytosol and nucleoplasm. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLK	NM_016231.5	c.459-36805T>C		intron_variant	Intron 1 of 10	ENST00000407008.8	NP_057315.3
NLK	XM_005257988.3	c.459-36805T>C		intron_variant	Intron 1 of 9		XP_005258045.1
NLK	XR_001752526.3	n.656-36805T>C		intron_variant	Intron 1 of 8
NLK	XR_934482.2	n.656-36805T>C		intron_variant	Intron 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLK	ENST00000407008.8	c.459-36805T>C		intron_variant	Intron 1 of 10	1	NM_016231.5	ENSP00000384625.3
NLK	ENST00000496808.1	n.303-36805T>C		intron_variant	Intron 1 of 11	2		ENSP00000433117.1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9244 AN: 152042 Hom.: 359 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0623

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0608 AC: 9254 AN: 152158 Hom.: 361 Cov.: 32 AF XY: 0.0613 AC XY: 4560 AN XY: 74410

African (AFR) AF: 0.0227 AC: 943 AN: 41520

American (AMR) AF: 0.0693 AC: 1060 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3468

East Asian (EAS) AF: 0.103 AC: 533 AN: 5162

South Asian (SAS) AF: 0.170 AC: 819 AN: 4822

European-Finnish (FIN) AF: 0.0353 AC: 374 AN: 10604

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0742 AC: 5047 AN: 67982

Other (OTH) AF: 0.0621 AC: 131 AN: 2108

Alfa AF: 0.0707 Hom.: 1716

Bravo AF: 0.0583

Asia WGS AF: 0.108 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		0.78
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: rs4420579; hg19: chr17-26412824;