rs12058769

Positions:

• chr1-198207593-T-C
• chr1-198207593-T-G

Variant summary

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

The NM_133494.3(NEK7):​c.-28-24960T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,990 control chromosomes in the GnomAD database, including 9,847 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 0.34 (9847 hom., cov: 32)
• Consequence: NEK7 NM_133494.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

NEK7 (HGNC:13386): (NIMA related kinase 7) NIMA-related kinases share high amino acid sequence identity with the gene product of the Aspergillus nidulans 'never in mitosis A' gene, which controls initiation of mitosis.[supplied by OMIM, Jul 2002]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK7	NM_133494.3	c.-28-24960T>C		intron_variant		ENST00000367385.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK7	ENST00000367385.9	c.-28-24960T>C		intron_variant		5	NM_133494.3	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51136 AN: 151872 Hom.: 9838 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.337 AC: 51177 AN: 151990 Hom.: 9847 Cov.: 32 AF XY: 0.346 AC XY: 25701 AN XY: 74294

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.332

Alfa AF: 0.282 Hom.: 819

Bravo AF: 0.347

Asia WGS AF: 0.606 AC: 2104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.73

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: rs12058769; hg19: chr1-198176723; COSMIC: COSV66311276; COSMIC: COSV66311276;