rs455567

Positions:

• chr6-33284338-G-A

Variant summary

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

The ENST00000374617.9(WDR46):​c.1115+2457C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 153,620 control chromosomes in the GnomAD database, including 27,644 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 (27419 hom., cov: 32)
  • Exomes 𝑓: 0.52 (225 hom.)
• Consequence: WDR46 ENST00000374617.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR46	NM_005452.6	c.1115+2457C>T		intron_variant		ENST00000374617.9	NP_005443.3
WDR46	NM_001164267.2	c.953+2457C>T		intron_variant			NP_001157739.1
WDR46	XM_047419523.1	c.1111+2461C>T		intron_variant			XP_047275479.1
WDR46	XM_047419524.1	c.1111+2461C>T		intron_variant			XP_047275480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR46	ENST00000374617.9	c.1115+2457C>T		intron_variant		1	NM_005452.6	ENSP00000363746	P1
WDR46	ENST00000444176.1	c.896+2457C>T		intron_variant		5		ENSP00000405568
WDR46	ENST00000489905.1	n.311+2457C>T		intron_variant, non_coding_transcript_variant		5
B3GALT4	ENST00000606990.1	n.314-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 90000 AN: 151942 Hom.: 27368 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.522 AC: 815 AN: 1560 Hom.: 225 Cov.: 0 AF XY: 0.535 AC XY: 433 AN XY: 810

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.593 AC: 90104 AN: 152060 Hom.: 27419 Cov.: 32 AF XY: 0.593 AC XY: 44049 AN XY: 74342

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.587

Alfa AF: 0.541 Hom.: 39533

Bravo AF: 0.601

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.49

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: rs455567; hg19: chr6-33252115;