rs630075

chr1-9310852-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• 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/exons	MANE	UniProt
SPSB1	NM_025106.4	c.-150+17781A>G		intron_variant		ENST00000328089.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPSB1	ENST00000328089.11	c.-150+17781A>G		intron_variant		1	NM_025106.4	P1
SPSB1	ENST00000450402.1	c.-150+16258A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.595

Alfa AF: 0.673 Hom.: 59998

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

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: rs630075; hg19: chr1-9370911; COSMIC: COSV60164682;