Variant chr5-37701062-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_018034.4(WDR70):c.1197C>T(p.Asp399=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,605,966 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 27 hom. )

Consequence

WDR70
NM_018034.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.58

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

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 5-37701062-C-T is Benign according to our data. Variant chr5-37701062-C-T is described in ClinVar as [Benign]. Clinvar id is 785120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.58 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1689/152180) while in subpopulation AFR AF= 0.0386 (1602/41514). AF 95% confidence interval is 0.037. There are 47 homozygotes in gnomad4. There are 788 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR70	NM_018034.4 linkuse as main transcript	c.1197C>T	p.Asp399=	synonymous_variant	12/18	ENST00000265107.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WDR70	ENST00000265107.9 linkuse as main transcript	c.1197C>T	p.Asp399=	synonymous_variant	12/18	1	NM_018034.4	P1
WDR70	ENST00000510699.1 linkuse as main transcript	n.554C>T		non_coding_transcript_exon_variant	6/7	5
WDR70	ENST00000511906.5 linkuse as main transcript	n.1211C>T		non_coding_transcript_exon_variant	11/15	2

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1688

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00275

AC:

691

AN:

251124

Hom.:

AF XY:

0.00206

AC XY:

280

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.0364

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00109

AC:

1591

AN:

1453786

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

701

AN XY:

723914

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000929

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.0111

AC:

1689

AN:

152180

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

788

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0386

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00462

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over