Variant rs446735 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005452.6(WDR46):c.879+29T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,611,646 control chromosomes in the GnomAD database, including 238,963 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 27002 hom., cov: 27)

Exomes 𝑓: 0.54 ( 211961 hom. )

Consequence

WDR46
NM_005452.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.314

Variant links:

Genes affected

WDR46 (HGNC:13923): (WD repeat domain 46) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

WDR46 links:

MIR6873 (HGNC:50231): (microRNA 6873) 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]

MIR6873 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR46	NM_005452.6 linkuse as main transcript	c.879+29T>G		intron_variant		ENST00000374617.9
MIR6873	NR_106933.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR46	ENST00000374617.9 linkuse as main transcript	c.879+29T>G		intron_variant		1	NM_005452.6	P1
MIR6873	ENST00000622788.1 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

88759

AN:

150064

Hom.:

26949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.736

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.590

GnomAD3 exomes

AF:

0.555

AC:

139269

AN:

251104

Hom.:

39558

AF XY:

0.557

AC XY:

75616

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.751

Gnomad AMR exome

AF:

0.534

Gnomad ASJ exome

AF:

0.597

Gnomad EAS exome

AF:

0.368

Gnomad SAS exome

AF:

0.627

Gnomad FIN exome

AF:

0.528

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.569

GnomAD4 exome

AF:

0.535

AC:

782290

AN:

1461464

Hom.:

211961

Cov.:

AF XY:

0.539

AC XY:

391493

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.747

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.599

Gnomad4 EAS exome

AF:

0.350

Gnomad4 SAS exome

AF:

0.626

Gnomad4 FIN exome

AF:

0.529

Gnomad4 NFE exome

AF:

0.526

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.592

AC:

88865

AN:

150182

Hom.:

27002

Cov.:

AF XY:

0.592

AC XY:

43281

AN XY:

73150

show subpopulations

Gnomad4 AFR

AF:

0.737

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.608

Gnomad4 EAS

AF:

0.391

Gnomad4 SAS

AF:

0.619

Gnomad4 FIN

AF:

0.525

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.587

Alfa

AF:

0.557

Hom.:

15658

Bravo

AF:

0.600

Asia WGS

AF:

0.514

AC:

1789

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.4

DANN

Benign

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over