rs1299374

Positions:

• chr1-9352349-A-G
• chr1-9352349-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPSB1	NM_025106.4	c.-149-3394A>G		intron_variant		ENST00000328089.11	NP_079382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPSB1	ENST00000328089.11	c.-149-3394A>G		intron_variant		1	NM_025106.4	ENSP00000330221	P1
SPSB1	ENST00000357898.3	c.-150+739A>G		intron_variant		5		ENSP00000350573	P1
SPSB1	ENST00000450402.1	c.-149-3394A>G		intron_variant		5		ENSP00000409235

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

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.833

Alfa AF: 0.825 Hom.: 67421

Bravo AF: 0.823

Asia WGS AF: 0.897 AC: 3117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.84

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: rs1299374; hg19: chr1-9412408; COSMIC: COSV60162507; COSMIC: COSV60162507;