1-9353587-C-T

Variant names:

• chr1-9353587-C-T
• rs11121384
• NM_025106.4:c.-149-2156C>T

Variant summary

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

The NM_025106.4(SPSB1):​c.-149-2156C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,052 control chromosomes in the GnomAD database, including 5,475 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 0.25 (5475 hom., cov: 31)
• Consequence: SPSB1 NM_025106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB1	NM_025106.4	MANE Select	c.-149-2156C>T		intron	N/A	NP_079382.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB1	ENST00000328089.11	TSL:1 MANE Select	c.-149-2156C>T		intron	N/A	ENSP00000330221.6
	SPSB1	ENST00000357898.3	TSL:5	c.-150+1977C>T		intron	N/A	ENSP00000350573.3
	SPSB1	ENST00000450402.1	TSL:5	c.-149-2156C>T		intron	N/A	ENSP00000409235.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37286 AN: 151934 Hom.: 5472 Cov.: 31

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.245 AC: 37290 AN: 152052 Hom.: 5475 Cov.: 31 AF XY: 0.243 AC XY: 18081 AN XY: 74316

African (AFR) AF: 0.0936 AC: 3886 AN: 41522

American (AMR) AF: 0.197 AC: 3016 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 951 AN: 3464

East Asian (EAS) AF: 0.285 AC: 1467 AN: 5154

South Asian (SAS) AF: 0.203 AC: 980 AN: 4830

European-Finnish (FIN) AF: 0.341 AC: 3596 AN: 10554

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22508 AN: 67926

Other (OTH) AF: 0.255 AC: 540 AN: 2114

Alfa AF: 0.303 Hom.: 12273

Bravo AF: 0.234

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.0
DANN	Benign	0.76
PhyloP100		-0.19
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: rs11121384; hg19: chr1-9413646; COSMIC: COSV60162514; COSMIC: COSV60162514;