rs630075

Variant names:

• chr1-9310852-A-G
• rs630075
• NM_025106.4:c.-150+17781A>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+17781A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,008 control chromosomes in the GnomAD database, including 27,232 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 0.59 (27232 hom., cov: 32)
• Consequence: SPSB1 NM_025106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPSB1	NM_025106.4	c.-150+17781A>G		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.-150+17781A>G		intron_variant	Intron 1 of 2	1	NM_025106.4	ENSP00000330221.6
SPSB1	ENST00000450402.1	c.-150+16258A>G		intron_variant	Intron 1 of 1	5		ENSP00000409235.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89192 AN: 151890 Hom.: 27227 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.587 AC: 89229 AN: 152008 Hom.: 27232 Cov.: 32 AF XY: 0.580 AC XY: 43119 AN XY: 74300

African (AFR) AF: 0.437 AC: 18096 AN: 41436

American (AMR) AF: 0.612 AC: 9344 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1544 AN: 5168

South Asian (SAS) AF: 0.655 AC: 3161 AN: 4826

European-Finnish (FIN) AF: 0.529 AC: 5581 AN: 10554

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46994 AN: 67968

Other (OTH) AF: 0.595 AC: 1257 AN: 2114

Alfa AF: 0.658 Hom.: 131100

Bravo AF: 0.586

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.8
DANN	Benign	0.36
PhyloP100		0.50
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: rs630075; hg19: chr1-9370911; COSMIC: COSV60164682;