rs469064

Positions:

• chr6-33282699-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005452.6(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 NM_005452.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR46	NM_005452.6	c.1116-1712G>T		intron_variant		ENST00000374617.9
WDR46	NM_001164267.2	c.954-1712G>T		intron_variant
WDR46	XM_047419523.1	c.1112-2177G>T		intron_variant
WDR46	XM_047419524.1	c.1112-1712G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR46	ENST00000374617.9	c.1116-1712G>T		intron_variant		1	NM_005452.6	P1
WDR46	ENST00000444176.1	c.897-1712G>T		intron_variant		5
WDR46	ENST00000489905.1	n.312-1712G>T		intron_variant, non_coding_transcript_variant		5
B3GALT4	ENST00000606990.1	n.314-1647C>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.446

Alfa AF: 0.501 Hom.: 27019

Bravo AF: 0.424

Asia WGS AF: 0.465 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.69

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: rs469064; hg19: chr6-33250476;