rs455567

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005452.6(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
NM_005452.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.197

Publications

29 publications found

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:

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]

B3GALT4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
WDR46	NM_005452.6 link	c.1115+2457C>T	intron_variant	Intron 10 of 14	ENST00000374617.9	NP_005443.3	O15213A8K806
WDR46	NM_001164267.2 link	c.953+2457C>T	intron_variant	Intron 10 of 14		NP_001157739.1	O15213A8K806B4DP15A0A1U9X8W1
WDR46	XM_047419523.1 link	c.1111+2461C>T	intron_variant	Intron 10 of 13		XP_047275479.1
WDR46	XM_047419524.1 link	c.1111+2461C>T	intron_variant	Intron 10 of 10		XP_047275480.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WDR46	ENST00000374617.9 link	c.1115+2457C>T	intron_variant	Intron 10 of 14	1	NM_005452.6	ENSP00000363746.4	O15213
WDR46	ENST00000444176.1 link	c.896+2457C>T	intron_variant	Intron 9 of 9	5		ENSP00000405568.1	H0Y6G3
WDR46	ENST00000489905.1 link	n.311+2457C>T	intron_variant	Intron 3 of 5	5
B3GALT4	ENST00000606990.1 link	n.314-8G>A	splice_region_variant, intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

90000

AN:

151942

Hom.:

27368

Cov.:

show subpopulations

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.:

AF XY:

0.535

AC XY:

433

AN XY:

810

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.526

AC:

805

AN:

1530

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.438

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.593

AC:

90104

AN:

152060

Hom.:

27419

Cov.:

AF XY:

0.593

AC XY:

44049

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.739

AC:

30618

AN:

41458

American (AMR)

AF:

0.579

AC:

8844

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2104

AN:

3468

East Asian (EAS)

AF:

0.392

AC:

2033

AN:

5182

South Asian (SAS)

AF:

0.623

AC:

2999

AN:

4816

European-Finnish (FIN)

AF:

0.527

AC:

5563

AN:

10558

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.532

AC:

36187

AN:

67988

Other (OTH)

AF:

0.587

AC:

1238

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1830

3659

5489

7318

9148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.551

Hom.:

94796

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

(source)

DANN

Benign

0.49

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over