rs6849776

chr4-169371841-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000687054.1(NEK1):n.4342-2037T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,464 control chromosomes in the GnomAD database, including 10,188 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 0.36 (10188 hom., cov: 29)
• Consequence: NEK1 ENST00000687054.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK1	ENST00000687054.1	n.4342-2037T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54226 AN: 151346 Hom.: 10165 Cov.: 29

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.358 AC: 54292 AN: 151464 Hom.: 10188 Cov.: 29 AF XY: 0.357 AC XY: 26451 AN XY: 74010

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0469

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.337

Alfa AF: 0.361 Hom.: 5513

Bravo AF: 0.355

Asia WGS AF: 0.282 AC: 983 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.2
Dann	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6849776; hg19: chr4-170292992;