rs12306

Variant names:

• chr17-27295085-G-T
• rs12306
• NM_015626.10:c.40+650G>T

Variant summary

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

The NM_015626.10(WSB1):​c.40+650G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,042 control chromosomes in the GnomAD database, including 8,633 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 0.33 (8633 hom., cov: 33)
• Consequence: WSB1 NM_015626.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 9 publications found

Genes affected

WSB1 (HGNC:19221): (WD repeat and SOCS box containing 1) This gene encodes a member of the WD-protein subfamily. This protein shares a high sequence identity to mouse and chick proteins. It contains several WD-repeats spanning most of the protein and an SOCS box in the C-terminus. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WSB1	NM_015626.10	c.40+650G>T		intron_variant	Intron 1 of 8	ENST00000262394.7	NP_056441.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WSB1	ENST00000262394.7	c.40+650G>T		intron_variant	Intron 1 of 8	1	NM_015626.10	ENSP00000262394.2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50303 AN: 151924 Hom.: 8630 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.331 AC: 50329 AN: 152042 Hom.: 8633 Cov.: 33 AF XY: 0.331 AC XY: 24606 AN XY: 74338

African (AFR) AF: 0.240 AC: 9944 AN: 41478

American (AMR) AF: 0.368 AC: 5618 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1444 AN: 5172

South Asian (SAS) AF: 0.409 AC: 1971 AN: 4818

European-Finnish (FIN) AF: 0.315 AC: 3335 AN: 10578

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24858 AN: 67930

Other (OTH) AF: 0.366 AC: 772 AN: 2112

Alfa AF: 0.357 Hom.: 4035

Bravo AF: 0.332

Asia WGS AF: 0.342 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.34
PhyloP100		0.19
Mutation Taster		=98/2	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: rs12306; hg19: chr17-25622111;