1-9327252-T-C

Variant names:

• chr1-9327252-T-C
• rs4908842
• NM_025106.4:c.-149-28491T>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.-149-28491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,074 control chromosomes in the GnomAD database, including 18,730 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 0.48 (18730 hom., cov: 32)
• Consequence: SPSB1 NM_025106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580
• Publications: 3 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]

ENSG00000294252 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB1	NM_025106.4	MANE Select	c.-149-28491T>C		intron	N/A	NP_079382.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB1	ENST00000328089.11	TSL:1 MANE Select	c.-149-28491T>C		intron	N/A	ENSP00000330221.6
	SPSB1	ENST00000450402.1	TSL:5	c.-149-28491T>C		intron	N/A	ENSP00000409235.1
	ENSG00000294252	ENST00000722150.1		n.121-5602A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72714 AN: 151954 Hom.: 18734 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.478 AC: 72717 AN: 152074 Hom.: 18730 Cov.: 32 AF XY: 0.468 AC XY: 34808 AN XY: 74340

African (AFR) AF: 0.310 AC: 12873 AN: 41484

American (AMR) AF: 0.476 AC: 7273 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1948 AN: 3472

East Asian (EAS) AF: 0.255 AC: 1321 AN: 5172

South Asian (SAS) AF: 0.532 AC: 2564 AN: 4822

European-Finnish (FIN) AF: 0.414 AC: 4373 AN: 10558

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40562 AN: 67962

Other (OTH) AF: 0.512 AC: 1080 AN: 2110

Alfa AF: 0.568 Hom.: 46160

Bravo AF: 0.475

Asia WGS AF: 0.379 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		0.58
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: rs4908842; hg19: chr1-9387311;