4-169394721-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001199397.3(NEK1):c.3848-198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,950 control chromosomes in the GnomAD database, including 10,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (10174 hom., cov: 33)
• Consequence: NEK1 NM_001199397.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.608

Genes affected

NEK1 (HGNC:7744): (NIMA related kinase 1) The protein encoded by this gene is a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. Defects in this gene are a cause of polycystic kidney disease (PKD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-169394721-G-A is Benign according to our data. Variant chr4-169394721-G-A is described in ClinVar as [Benign]. Clinvar id is 667932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK1	NM_001199397.3	c.3848-198C>T		intron_variant		ENST00000507142.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK1	ENST00000507142.6	c.3848-198C>T		intron_variant		1	NM_001199397.3	A2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54287 AN: 151832 Hom.: 10151 Cov.: 33

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0678

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.358 AC: 54353 AN: 151950 Hom.: 10174 Cov.: 33 AF XY: 0.357 AC XY: 26521 AN XY: 74284

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0678

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.332

Alfa AF: 0.353 Hom.: 2302

Bravo AF: 0.354

Asia WGS AF: 0.287 AC: 999 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.38
Dann	Benign	0.17

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: rs13131146; hg19: chr4-170315872;