Genetic Variant NM_003390.4:c.1141+1133A>G (chr11-9578396-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003390.4(WEE1):c.1141+1133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 154,426 control chromosomes in the GnomAD database, including 15,752 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 0.45 ( 15485 hom., cov: 33)

Exomes 𝑓: 0.46 ( 267 hom. )

Consequence

WEE1
NM_003390.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.967

Publications

11 publications found

Variant links:

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]

WEE1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
WEE1	NM_003390.4 link	c.1141+1133A>G	intron_variant	Intron 5 of 10	ENST00000450114.7	NP_003381.1	P30291-1Q86V29
WEE1	NM_001143976.2 link	c.499+1133A>G	intron_variant	Intron 5 of 10		NP_001137448.1	P30291-2
WEE1	XM_047427539.1 link	c.499+1133A>G	intron_variant	Intron 5 of 10		XP_047283495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WEE1	ENST00000450114.7 link	c.1141+1133A>G		intron_variant	Intron 5 of 10	1	NM_003390.4	ENSP00000402084.2		P30291-1

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67806

AN:

151894

Hom.:

15479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.618

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.499

GnomAD4 exome

AF:

0.460

AC:

1111

AN:

2414

Hom.:

267

Cov.:

AF XY:

0.464

AC XY:

582

AN XY:

1254

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.639

AC:

AN:

122

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.650

AC:

AN:

South Asian (SAS)

AF:

0.419

AC:

AN:

172

European-Finnish (FIN)

AF:

0.500

AC:

AN:

130

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.440

AC:

765

AN:

1740

Other (OTH)

AF:

0.500

AC:

AN:

162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.446

AC:

67840

AN:

152012

Hom.:

15485

Cov.:

AF XY:

0.445

AC XY:

33077

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.475

AC:

19682

AN:

41446

American (AMR)

AF:

0.507

AC:

7741

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

1587

AN:

3468

East Asian (EAS)

AF:

0.618

AC:

3200

AN:

5178

South Asian (SAS)

AF:

0.392

AC:

1894

AN:

4828

European-Finnish (FIN)

AF:

0.413

AC:

4364

AN:

10560

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.409

AC:

27785

AN:

67952

Other (OTH)

AF:

0.500

AC:

1054

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1908

3816

5724

7632

9540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.435

Hom.:

14393

Bravo

AF:

0.462

Asia WGS

AF:

0.510

AC:

1768

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.94

(source)

DANN

Benign

0.70

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over