1-9327252-T-C

Position:

• chr1-9327252-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPSB1	NM_025106.4	c.-149-28491T>C		intron_variant		ENST00000328089.11	NP_079382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPSB1	ENST00000328089.11	c.-149-28491T>C		intron_variant		1	NM_025106.4	ENSP00000330221	P1
SPSB1	ENST00000450402.1	c.-149-28491T>C		intron_variant		5		ENSP00000409235

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

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.512

Alfa AF: 0.584 Hom.: 34891

Bravo AF: 0.475

Asia WGS AF: 0.379 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.62

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: rs4908842; hg19: chr1-9387311;