Genetic Variant WDR70:c.493-1427C>G (chr5-37436495-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018034.4(WDR70):c.493-1427C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 152,186 control chromosomes in the GnomAD database, including 132 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 0.034 ( 132 hom., cov: 32)

Consequence

WDR70
NM_018034.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0970

Publications

0 publications found

Variant links:

Genes affected

WDR70 (HGNC:25495): (WD repeat domain 70) Enables enzyme binding activity. Predicted to be involved in regulation of DNA double-strand break processing and regulation of histone H2B conserved C-terminal lysine ubiquitination. Predicted to be active in nucleus and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

WDR70 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_018034.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.74).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018034.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR70	NM_018034.4	MANE Select	c.493-1427C>G	intron	N/A	NP_060504.1	Q9NW82
WDR70	NM_001345998.2		c.490-1427C>G	intron	N/A	NP_001332927.1
WDR70	NM_001345999.2		c.427-1427C>G	intron	N/A	NP_001332928.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR70	ENST00000265107.9	TSL:1 MANE Select	c.493-1427C>G	intron	N/A	ENSP00000265107.4	Q9NW82
WDR70	ENST00000504564.1	TSL:1	c.493-1427C>G	intron	N/A	ENSP00000425841.1	D6RIW8
WDR70	ENST00000863541.1		c.490-1427C>G	intron	N/A	ENSP00000533600.1

Frequencies

GnomAD3 genomes

AF:

0.0336

AC:

5108

AN:

152068

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0710

Gnomad ASJ

AF:

0.0398

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.0654

Gnomad FIN

AF:

0.0570

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0297

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

GnomAD4 genome

AF:

0.0337

AC:

5123

AN:

152186

Hom.:

132

Cov.:

AF XY:

0.0351

AC XY:

2611

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0162

AC:

674

AN:

41540

American (AMR)

AF:

0.0713

AC:

1091

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0398

AC:

138

AN:

3468

East Asian (EAS)

AF:

0.00309

AC:

AN:

5186

South Asian (SAS)

AF:

0.0661

AC:

318

AN:

4810

European-Finnish (FIN)

AF:

0.0570

AC:

604

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0325

AC:

2207

AN:

67980

Other (OTH)

AF:

0.0317

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

253

506

759

1012

1265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0327

Hom.:

Bravo

AF:

0.0329

Asia WGS

AF:

0.0620

AC:

216

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.5

(source)

DANN

Benign

0.73

PhyloP100

0.097

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over