ENST00000687054.1:n.4342-2037T>C

Variant names:

• chr4-169371841-A-G
• rs6849776
• ENST00000687054.1:n.4342-2037T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000687054.1(NEK1):​n.4342-2037T>C 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 151,464 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 0 publications found

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]

NEK1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis, susceptibility to, 24

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
• short-rib thoracic dysplasia 6 with or without polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• orofaciodigital syndrome type II

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Majewski type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK1	ENST00000687054.1	n.4342-2037T>C		intron_variant	Intron 34 of 34

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

African (AFR) AF: 0.437 AC: 17989 AN: 41204

American (AMR) AF: 0.308 AC: 4684 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1032 AN: 3466

East Asian (EAS) AF: 0.0469 AC: 243 AN: 5184

South Asian (SAS) AF: 0.459 AC: 2198 AN: 4792

European-Finnish (FIN) AF: 0.290 AC: 3023 AN: 10416

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23972 AN: 67898

Other (OTH) AF: 0.337 AC: 706 AN: 2096

Alfa AF: 0.361 Hom.: 6068

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
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs6849776; hg19: chr4-170292992;