rs2718874

Positions:

• chr3-131156204-A-G

Variant summary

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

The NM_024800.5(NEK11):​c.962+1083A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 152,186 control chromosomes in the GnomAD database, including 1,138 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 0.091 (1138 hom., cov: 32)
• Consequence: NEK11 NM_024800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

Genes affected

NEK11 (HGNC:18593): (NIMA related kinase 11) This gene encodes a member of the never in mitosis gene A family of kinases. The encoded protein localizes to the nucleoli, and may function with NEK2A in the S-phase checkpoint. The encoded protein appears to play roles in DNA replication and response to genotoxic stress. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK11	NM_024800.5	c.962+1083A>G		intron_variant		ENST00000383366.9	NP_079076.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK11	ENST00000383366.9	c.962+1083A>G		intron_variant		1	NM_024800.5	ENSP00000372857	P1

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13767 AN: 152068 Hom.: 1131 Cov.: 32

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0506

Gnomad OTH AF: 0.0926

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

GnomAD4 genome AF: 0.0906 AC: 13792 AN: 152186 Hom.: 1138 Cov.: 32 AF XY: 0.0970 AC XY: 7214 AN XY: 74408

Gnomad4 AFR AF: 0.0879

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.0907

Gnomad4 FIN AF: 0.0730

Gnomad4 NFE AF: 0.0506

Gnomad4 OTH AF: 0.0931

Alfa AF: 0.0839 Hom.: 165

Bravo AF: 0.104

Asia WGS AF: 0.229 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
DANN	Benign	0.67

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: rs2718874; hg19: chr3-130875048;