rs2125846

chr17-28171022-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.1048-1495T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,156 control chromosomes in the GnomAD database, including 2,869 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 0.19 (2869 hom., cov: 32)
• Consequence: NLK NM_016231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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

Verdict is Benign. Variant got -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 = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLK	NM_016231.5	c.1048-1495T>C		intron_variant		ENST00000407008.8
NLK	XM_005257988.3	c.1048-1495T>C		intron_variant
NLK	XR_001752526.3	n.1245-1495T>C		intron_variant, non_coding_transcript_variant
NLK	XR_934482.2	n.1245-1495T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLK	ENST00000407008.8	c.1048-1495T>C		intron_variant		1	NM_016231.5	P1
NLK	ENST00000496808.1	c.892-1495T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28925 AN: 152038 Hom.: 2863 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.190 AC: 28951 AN: 152156 Hom.: 2869 Cov.: 32 AF XY: 0.191 AC XY: 14189 AN XY: 74362

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.204

Alfa AF: 0.196 Hom.: 875

Bravo AF: 0.185

Asia WGS AF: 0.305 AC: 1059 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	1.5
Dann	Benign	0.62

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: rs2125846; hg19: chr17-26498048;