rs4420579

Positions:

• chr17-28085798-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

NLK (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NLK	NM_016231.5	c.459-36805T>C		intron_variant		ENST00000407008.8	NP_057315.3
NLK	XM_005257988.3	c.459-36805T>C		intron_variant			XP_005258045.1
NLK	XR_001752526.3	n.656-36805T>C		intron_variant
NLK	XR_934482.2	n.656-36805T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLK	ENST00000407008.8	c.459-36805T>C		intron_variant		1	NM_016231.5	ENSP00000384625.3
NLK	ENST00000496808.1	n.303-36805T>C		intron_variant		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

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.0693

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0742

Gnomad4 OTH AF: 0.0621

Alfa AF: 0.0728 Hom.: 721

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

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: rs4420579; hg19: chr17-26412824;