dbSNP rs11121382: SPSB1:c.-149-4333G>C (chr1-9351410-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025106.4(SPSB1):c.-149-4333G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,250 control chromosomes in the GnomAD database, including 5,282 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 0.23 ( 5279 hom., cov: 33)

Exomes 𝑓: 0.39 ( 3 hom. )

Consequence

SPSB1
NM_025106.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0870

Publications

7 publications found

Variant links:

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]

SPSB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPSB1	NM_025106.4 link	c.-149-4333G>C		intron_variant	Intron 1 of 2	ENST00000328089.11	NP_079382.2	Q96BD6A0A024R4G8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPSB1	ENST00000328089.11 link	c.-149-4333G>C	intron_variant	Intron 1 of 2	1	NM_025106.4	ENSP00000330221.6	Q96BD6
SPSB1	ENST00000450402.1 link	c.-149-4333G>C	intron_variant	Intron 1 of 1	5		ENSP00000409235.1	A2A276
SPSB1	ENST00000357898.3 link	c.-350G>C	upstream_gene_variant		5		ENSP00000350573.3	Q96BD6

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35707

AN:

152092

Hom.:

5279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0639

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.395

AC:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.286

AC:

AN:

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.235

AC:

35702

AN:

152212

Hom.:

5279

Cov.:

AF XY:

0.230

AC XY:

17129

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0637

AC:

2648

AN:

41548

American (AMR)

AF:

0.182

AC:

2781

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1186

AN:

3472

East Asian (EAS)

AF:

0.295

AC:

1525

AN:

5170

South Asian (SAS)

AF:

0.197

AC:

951

AN:

4826

European-Finnish (FIN)

AF:

0.310

AC:

3286

AN:

10604

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.330

AC:

22456

AN:

67984

Other (OTH)

AF:

0.242

AC:

512

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1330

2659

3989

5318

6648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.316

Hom.:

4525

Bravo

AF:

0.220

Asia WGS

AF:

0.220

AC:

765

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.4

(source)

DANN

Benign

0.76

PhyloP100

0.087

PromoterAI

0.016

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over