rs2125846

Variant names:

• chr17-28171022-T-C
• rs2125846
• NM_016231.5:c.1048-1495T>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.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
• Publications: 6 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]

ENSG00000301334 (HGNC:):

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 = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLK	NM_016231.5	c.1048-1495T>C		intron_variant	Intron 6 of 10	ENST00000407008.8	NP_057315.3
NLK	XM_005257988.3	c.1048-1495T>C		intron_variant	Intron 6 of 9		XP_005258045.1
NLK	XR_001752526.3	n.1245-1495T>C		intron_variant	Intron 6 of 8
NLK	XR_934482.2	n.1245-1495T>C		intron_variant	Intron 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLK	ENST00000407008.8	c.1048-1495T>C		intron_variant	Intron 6 of 10	1	NM_016231.5	ENSP00000384625.3
NLK	ENST00000496808.1	n.892-1495T>C		intron_variant	Intron 6 of 11	2		ENSP00000433117.1
ENSG00000301334	ENST00000778042.1	n.162-18468A>G		intron_variant	Intron 2 of 2
NLK	ENST00000584188.1	n.-211T>C		upstream_gene_variant		3

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

African (AFR) AF: 0.147 AC: 6124 AN: 41526

American (AMR) AF: 0.163 AC: 2489 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1775 AN: 5174

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1704 AN: 10578

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14064 AN: 67980

Other (OTH) AF: 0.204 AC: 431 AN: 2114

Alfa AF: 0.202 Hom.: 1466

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
PhyloP100		-0.041
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: rs2125846; hg19: chr17-26498048;