Genetic Variant 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.

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.-149-4333G>C		intron	N/A	NP_079382.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SPSB1	ENST00000328089.11	TSL:1 MANE Select	c.-149-4333G>C	intron	N/A	ENSP00000330221.6
SPSB1	ENST00000450402.1	TSL:5	c.-149-4333G>C	intron	N/A	ENSP00000409235.1
SPSB1	ENST00000357898.3	TSL:5	c.-350G>C	upstream_gene	N/A	ENSP00000350573.3

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over