rs2241469

chr4-10078838-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.528

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]

ACMG classification

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/exons	MANE	UniProt
WDR1	NM_017491.5	c.1395+53T>G		intron_variant		ENST00000499869.7
WDR1	NM_005112.5	c.975+53T>G		intron_variant
WDR1	XM_017008880.3	c.1554+53T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR1	ENST00000499869.7	c.1395+53T>G		intron_variant		5	NM_017491.5	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38124 AN: 151832 Hom.: 5079 Cov.: 33

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.: 19 AF XY: 0.295 AC XY: 197890 AN XY: 669764

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.: 33 AF XY: 0.254 AC XY: 18892 AN XY: 74268

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

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

Other links and lift over

dbSNP: rs2241469; hg19: chr4-10080462; COSMIC: COSV66723564; COSMIC: COSV66723564;