1-9352349-A-G

Variant names:

• chr1-9352349-A-G
• rs1299374
• NM_025106.4:c.-149-3394A>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.-149-3394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,154 control chromosomes in the GnomAD database, including 51,385 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 0.82 (51385 hom., cov: 32)
• Consequence: SPSB1 NM_025106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB1	NM_025106.4	MANE Select	c.-149-3394A>G		intron	N/A	NP_079382.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB1	ENST00000328089.11	TSL:1 MANE Select	c.-149-3394A>G		intron	N/A	ENSP00000330221.6	Q96BD6
	SPSB1	ENST00000357898.3	TSL:5	c.-150+739A>G		intron	N/A	ENSP00000350573.3	Q96BD6
	SPSB1	ENST00000852374.1		c.-149-3394A>G		intron	N/A	ENSP00000522433.1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124933 AN: 152036 Hom.: 51346 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.822 AC: 125028 AN: 152154 Hom.: 51385 Cov.: 32 AF XY: 0.824 AC XY: 61330 AN XY: 74398

African (AFR) AF: 0.795 AC: 32971 AN: 41486

American (AMR) AF: 0.838 AC: 12825 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2876 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4939 AN: 5164

South Asian (SAS) AF: 0.873 AC: 4204 AN: 4816

European-Finnish (FIN) AF: 0.818 AC: 8675 AN: 10608

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55749 AN: 67996

Other (OTH) AF: 0.833 AC: 1755 AN: 2108

Alfa AF: 0.822 Hom.: 96734

Bravo AF: 0.823

Asia WGS AF: 0.897 AC: 3117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.84
PhyloP100		-0.20
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: rs1299374; hg19: chr1-9412408; COSMIC: COSV60162507; COSMIC: COSV60162507;