4-39257570-A-G

Position:

chr4-39257570-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025132.4(WDR19):c.3183+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,561,466 control chromosomes in the GnomAD database, including 81,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8227 hom., cov: 31)

Exomes 𝑓: 0.32 ( 73046 hom. )

Consequence

WDR19
NM_025132.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.552

Variant links:

Genes affected

WDR19 (HGNC:18340): (WD repeat domain 19) The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

WDR19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-39257570-A-G is Benign according to our data. Variant chr4-39257570-A-G is described in ClinVar as [Benign]. Clinvar id is 261862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-39257570-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR19	NM_025132.4 linkuse as main transcript	c.3183+16A>G		intron_variant		ENST00000399820.8	NP_079408.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
WDR19	ENST00000399820.8 linkuse as main transcript	c.3183+16A>G	intron_variant	1	NM_025132.4	ENSP00000382717	P1	Q8NEZ3-1
WDR19	ENST00000506869.5 linkuse as main transcript	c.*2764+16A>G	intron_variant, NMD_transcript_variant	2		ENSP00000424319
WDR19	ENST00000512095.5 linkuse as main transcript	n.2181+16A>G	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49636

AN:

151930

Hom.:

8218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.311

AC:

55513

AN:

178276

Hom.:

8786

AF XY:

0.313

AC XY:

29509

AN XY:

94424

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.259

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.161

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.319

AC:

450252

AN:

1409418

Hom.:

73046

Cov.:

AF XY:

0.319

AC XY:

222188

AN XY:

696168

show subpopulations

Gnomad4 AFR exome

AF:

0.354

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.311

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.327

AC:

49658

AN:

152048

Hom.:

8227

Cov.:

AF XY:

0.326

AC XY:

24210

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.351

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.325

Hom.:

1761

Bravo

AF:

0.321

Asia WGS

AF:

0.223

AC:

777

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 13, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Nephronophthisis 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Senior-Loken syndrome 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Asphyxiating thoracic dystrophy 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cranioectodermal dysplasia 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Asphyxiating thoracic dystrophy 5;C4225376:Senior-Loken syndrome 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.11

DANN

Benign

0.32

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