rs2241469

Variant names:

• chr4-10078838-A-C
• rs2241469
• NM_017491.5:c.1395+53T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.1395+53T>G		intron_variant	Intron 12 of 14	ENST00000499869.7	NP_059830.1

Ensembl

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

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

African (AFR) AF: 0.158 AC: 4865 AN: 30710

American (AMR) AF: 0.283 AC: 11938 AN: 42172

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4047 AN: 23980

East Asian (EAS) AF: 0.378 AC: 14036 AN: 37088

South Asian (SAS) AF: 0.439 AC: 34786 AN: 79310

European-Finnish (FIN) AF: 0.299 AC: 15604 AN: 52258

Middle Eastern (MID) AF: 0.229 AC: 1260 AN: 5500

European-Non Finnish (NFE) AF: 0.285 AC: 288985 AN: 1015130

Other (OTH) AF: 0.270 AC: 15180 AN: 56132

GnomAD4 genome AF: 0.251 AC: 38131 AN: 151950 Hom.: 5081 Cov.: 33 AF XY: 0.254 AC XY: 18892 AN XY: 74268

African (AFR) AF: 0.168 AC: 6964 AN: 41498

American (AMR) AF: 0.234 AC: 3573 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1771 AN: 5090

South Asian (SAS) AF: 0.444 AC: 2138 AN: 4818

European-Finnish (FIN) AF: 0.308 AC: 3252 AN: 10558

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19180 AN: 67918

Other (OTH) AF: 0.235 AC: 496 AN: 2110

Alfa AF: 0.273 Hom.: 4880

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

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
PhyloP100		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=18/82	disease causing

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

Other links and lift over

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