rs1294028

chr1-9304575-A-Gchr1-9304575-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPSB1	NM_025106.4	c.-150+11504A>G		intron_variant		ENST00000328089.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPSB1	ENST00000328089.11	c.-150+11504A>G		intron_variant		1	NM_025106.4	P1
SPSB1	ENST00000450402.1	c.-150+9981A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.649

Alfa AF: 0.630 Hom.: 40532

Bravo AF: 0.634

Asia WGS AF: 0.727 AC: 2528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.4
Dann	Benign	0.42

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: rs1294028; hg19: chr1-9364634;