1-9304575-A-G

Variant names:

• chr1-9304575-A-G
• rs1294028
• NM_025106.4:c.-150+11504A>G

Variant summary

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

The NM_025106.4(SPSB1):​c.-150+11504A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,992 control chromosomes in the GnomAD database, including 29,945 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 0.63 (29945 hom., cov: 31)
• Consequence: SPSB1 NM_025106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 4 publications found

Genes affected

SPSB1 (HGNC:30628): (splA/ryanodine receptor domain and SOCS box containing 1) Enables ubiquitin ligase-substrate adaptor activity. Involved in protein ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025106.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB1	NM_025106.4	MANE Select	c.-150+11504A>G		intron	N/A	NP_079382.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB1	ENST00000328089.11	TSL:1 MANE Select	c.-150+11504A>G		intron	N/A	ENSP00000330221.6	Q96BD6
	SPSB1	ENST00000852374.1		c.-450-10902A>G		intron	N/A	ENSP00000522433.1
	SPSB1	ENST00000852375.1		c.-150+10791A>G		intron	N/A	ENSP00000522434.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95005 AN: 151874 Hom.: 29904 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.626 AC: 95099 AN: 151992 Hom.: 29945 Cov.: 31 AF XY: 0.626 AC XY: 46497 AN XY: 74292

African (AFR) AF: 0.585 AC: 24217 AN: 41424

American (AMR) AF: 0.694 AC: 10606 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2321 AN: 3470

East Asian (EAS) AF: 0.798 AC: 4117 AN: 5160

South Asian (SAS) AF: 0.666 AC: 3213 AN: 4822

European-Finnish (FIN) AF: 0.577 AC: 6096 AN: 10562

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42350 AN: 67966

Other (OTH) AF: 0.649 AC: 1369 AN: 2108

Alfa AF: 0.631 Hom.: 56318

Bravo AF: 0.634

Asia WGS AF: 0.727 AC: 2528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.4
DANN	Benign	0.42
PhyloP100		0.053
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: rs1294028; hg19: chr1-9364634;