Genetic Variant SPSB2:c.665-12_665-10delTCT (chr12-6871328-GAGA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_032641.4(SPSB2):c.665-12_665-10delTCT variant causes a intron change. The variant allele was found at a frequency of 0.0048 in 1,610,914 control chromosomes in the GnomAD database, including 295 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 161 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 134 hom. )

Consequence

SPSB2
NM_032641.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.61

Variant links:

Genes affected

SPSB2 (HGNC:29522): (splA/ryanodine receptor domain and SOCS box containing 2) This gene encodes a member of a subfamily of proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal suppressor of cytokine signaling (SOCS) box. This protein plays a role in cell signaling. This gene is present in a gene-rich cluster on chromosome 12p13 in the vicinity of the CD4 antigen and triosephosphate isomerase genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

SPSB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-6871328-GAGA-G is Benign according to our data. Variant chr12-6871328-GAGA-G is described in ClinVar as [Benign]. Clinvar id is 781241.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SPSB2	NM_032641.4 link	c.665-12_665-10delTCT	intron_variant	Intron 2 of 2	ENST00000524270.6	NP_116030.1	Q99619-1
SPSB2	NM_001146316.2 link	c.665-12_665-10delTCT	intron_variant	Intron 2 of 2		NP_001139788.1	Q99619-1
SPSB2	NM_001319670.2 link	c.665-12_665-10delTCT	intron_variant	Intron 1 of 1		NP_001306599.1	Q99619-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPSB2	ENST00000524270.6 link	c.665-12_665-10delTCT		intron_variant	Intron 2 of 2	1	NM_032641.4	ENSP00000428338.1		Q99619-1
SPSB2	ENST00000523102.5 link	c.665-12_665-10delTCT		intron_variant	Intron 2 of 2	1		ENSP00000430872.1		Q99619-1

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

3592

AN:

152214

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0815

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00712

AC:

1752

AN:

246126

Hom.:

AF XY:

0.00569

AC XY:

759

AN XY:

133312

show subpopulations

Gnomad AFR exome

AF:

0.0853

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0000664

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000504

Gnomad OTH exome

AF:

0.00317

GnomAD4 exome

AF:

0.00282

AC:

4106

AN:

1458582

Hom.:

134

AF XY:

0.00254

AC XY:

1841

AN XY:

725334

show subpopulations

Gnomad4 AFR exome

AF:

0.0833

Gnomad4 AMR exome

AF:

0.00462

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000251

Gnomad4 OTH exome

AF:

0.00546

GnomAD4 genome

AF:

0.0238

AC:

3619

AN:

152332

Hom.:

161

Cov.:

AF XY:

0.0227

AC XY:

1689

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0820

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 20, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over