rs11121382

Positions:

• chr1-9351410-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000328089.11(SPSB1):​c.-149-4333G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,250 control chromosomes in the GnomAD database, including 5,282 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 0.23 (5279 hom., cov: 33)
  • Exomes 𝑓: 0.39 (3 hom.)
• Consequence: SPSB1 ENST00000328089.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPSB1	NM_025106.4	c.-149-4333G>C		intron_variant		ENST00000328089.11	NP_079382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPSB1	ENST00000328089.11	c.-149-4333G>C		intron_variant		1	NM_025106.4	ENSP00000330221	P1
SPSB1	ENST00000450402.1	c.-149-4333G>C		intron_variant		5		ENSP00000409235
SPSB1	ENST00000357898.3			upstream_gene_variant		5		ENSP00000350573	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35707 AN: 152092 Hom.: 5279 Cov.: 33

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.395 AC: 15 AN: 38 Hom.: 3 Cov.: 0 AF XY: 0.375 AC XY: 6 AN XY: 16

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.235 AC: 35702 AN: 152212 Hom.: 5279 Cov.: 33 AF XY: 0.230 AC XY: 17129 AN XY: 74404

Gnomad4 AFR AF: 0.0637

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.242

Alfa AF: 0.316 Hom.: 4525

Bravo AF: 0.220

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.76

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: rs11121382; hg19: chr1-9411469;