dbSNP rs2241469: WDR1:c.1395+53T>G (chr4-10078838-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_017491.5(WDR1):c.1395+53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,494,230 control chromosomes in the GnomAD database, including 63,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5081 hom., cov: 33)

Exomes 𝑓: 0.29 ( 58912 hom. )

Consequence

WDR1
NM_017491.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.528

Variant links:

Genes affected

WDR1 (HGNC:12754): (WD repeat domain 1) This gene encodes a protein containing 9 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, mostly including a trp-asp at the C-terminal end. WD domains are involved in protein-protein interactions. The encoded protein may help induce the disassembly of actin filaments. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

WDR1 links:

MIR3138 (HGNC:38341): (microRNA 3138) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3138 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-10078838-A-C is Benign according to our data. Variant chr4-10078838-A-C is described in ClinVar as [Benign]. Clinvar id is 2688169.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR1	NM_017491.5 link	c.1395+53T>G		intron_variant	Intron 12 of 14	ENST00000499869.7	NP_059830.1	O75083-1V9HWG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR1	ENST00000499869.7 link	c.1395+53T>G		intron_variant	Intron 12 of 14	5	NM_017491.5	ENSP00000427687.1		O75083-1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38124

AN:

151832

Hom.:

5079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.291

AC:

390701

AN:

1342280

Hom.:

58912

Cov.:

AF XY:

0.295

AC XY:

197890

AN XY:

669764

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.283

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.378

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.251

AC:

38131

AN:

151950

Hom.:

5081

Cov.:

AF XY:

0.254

AC XY:

18892

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.444

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.281

Hom.:

3779

Bravo

AF:

0.238

Asia WGS

AF:

0.385

AC:

1335

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.1

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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