chr6-33282699-C-A

Variant names:

• chr6-33282699-C-A
• rs469064
• NM_005452.6:c.1116-1712G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374617.9(WDR46):​c.1116-1712G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,032 control chromosomes in the GnomAD database, including 15,845 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 0.44 (15845 hom., cov: 33)
• Consequence: WDR46 ENST00000374617.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 19 publications found

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]

B3GALT4 (HGNC:919): (beta-1,3-galactosyltransferase 4) This gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). This gene is oriented telomere to centromere in close proximity to the ribosomal protein S18 gene. The functionality of the encoded protein is limited to ganglioseries glycolipid biosynthesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374617.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR46	NM_005452.6	MANE Select	c.1116-1712G>T		intron	N/A	NP_005443.3
	WDR46	NM_001164267.2		c.954-1712G>T		intron	N/A	NP_001157739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR46	ENST00000374617.9	TSL:1 MANE Select	c.1116-1712G>T		intron	N/A	ENSP00000363746.4
	WDR46	ENST00000444176.1	TSL:5	c.897-1712G>T		intron	N/A	ENSP00000405568.1
	WDR46	ENST00000489905.1	TSL:5	n.312-1712G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66802 AN: 151914 Hom.: 15833 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66846 AN: 152032 Hom.: 15845 Cov.: 33 AF XY: 0.445 AC XY: 33041 AN XY: 74276

African (AFR) AF: 0.253 AC: 10494 AN: 41498

American (AMR) AF: 0.490 AC: 7487 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1867 AN: 3472

East Asian (EAS) AF: 0.386 AC: 1996 AN: 5172

South Asian (SAS) AF: 0.595 AC: 2864 AN: 4816

European-Finnish (FIN) AF: 0.525 AC: 5546 AN: 10562

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35196 AN: 67922

Other (OTH) AF: 0.446 AC: 941 AN: 2112

Alfa AF: 0.490 Hom.: 68293

Bravo AF: 0.424

Asia WGS AF: 0.465 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.69
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs469064; hg19: chr6-33250476;