rs4370932

chr11-9581689-C-T

Variant summary

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

The NM_003390.4(WEE1):c.1288+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,603,850 control chromosomes in the GnomAD database, including 116,168 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 0.40 (12630 hom., cov: 33)
  • Exomes 𝑓: 0.37 (103538 hom.)
• Consequence: WEE1 NM_003390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

Genes affected

WEE1 (HGNC:12761): (WEE1 G2 checkpoint kinase) This gene encodes a nuclear protein, which is a tyrosine kinase belonging to the Ser/Thr family of protein kinases. This protein catalyzes the inhibitory tyrosine phosphorylation of CDC2/cyclin B kinase, and appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from cytoplasmically activated CDC2 kinase. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE1	NM_003390.4	c.1288+11C>T		intron_variant		ENST00000450114.7
WEE1	NM_001143976.2	c.646+11C>T		intron_variant
WEE1	XM_047427539.1	c.646+11C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WEE1	ENST00000450114.7	c.1288+11C>T		intron_variant		1	NM_003390.4	P3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61088 AN: 151912 Hom.: 12625 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.445

GnomAD3 exomes AF: 0.408 AC: 99140 AN: 242772 Hom.: 20839 AF XY: 0.402 AC XY: 52821 AN XY: 131510

Gnomad AFR exome AF: 0.448

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.412

Gnomad EAS exome AF: 0.457

Gnomad SAS exome AF: 0.378

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.372

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.374 AC: 542981 AN: 1451820 Hom.: 103538 Cov.: 33 AF XY: 0.374 AC XY: 270119 AN XY: 722382

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.380

GnomAD4 genome AF: 0.402 AC: 61119 AN: 152030 Hom.: 12630 Cov.: 33 AF XY: 0.400 AC XY: 29760 AN XY: 74324

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.447

Alfa AF: 0.388 Hom.: 16729

Bravo AF: 0.419

Asia WGS AF: 0.415 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.0
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4370932; hg19: chr11-9603236;