rs11121380

Variant names:

• chr1-9348900-A-C
• rs11121380
• NM_025106.4:c.-149-6843A>C

Variant summary

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

The NM_025106.4(SPSB1):​c.-149-6843A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 151,966 control chromosomes in the GnomAD database, including 1,188 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 0.10 (1188 hom., cov: 31)
• Consequence: SPSB1 NM_025106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPSB1	NM_025106.4	c.-149-6843A>C		intron_variant	Intron 1 of 2	ENST00000328089.11	NP_079382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPSB1	ENST00000328089.11	c.-149-6843A>C		intron_variant	Intron 1 of 2	1	NM_025106.4	ENSP00000330221.6
SPSB1	ENST00000450402.1	c.-149-6843A>C		intron_variant	Intron 1 of 1	5		ENSP00000409235.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15456 AN: 151848 Hom.: 1187 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0964

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

GnomAD4 genome AF: 0.102 AC: 15472 AN: 151966 Hom.: 1188 Cov.: 31 AF XY: 0.0979 AC XY: 7269 AN XY: 74258

African (AFR) AF: 0.211 AC: 8756 AN: 41426

American (AMR) AF: 0.0757 AC: 1155 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.0270 AC: 130 AN: 4810

European-Finnish (FIN) AF: 0.0308 AC: 326 AN: 10572

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0680 AC: 4621 AN: 67978

Other (OTH) AF: 0.0954 AC: 201 AN: 2106

Alfa AF: 0.0802 Hom.: 1769

Bravo AF: 0.109

Asia WGS AF: 0.0200 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.29
PhyloP100		-0.10
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: rs11121380; hg19: chr1-9408959;