rs143871029

Variant names:

• chr12-6871328-GAGA-G
• rs143871029
• NM_032641.4:c.665-12_665-10delTCT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.61
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB2	NM_032641.4	MANE Select	c.665-12_665-10delTCT		intron	N/A	NP_116030.1	Q99619-1
	SPSB2	NM_001146316.2		c.665-12_665-10delTCT		intron	N/A	NP_001139788.1	Q99619-1
	SPSB2	NM_001319670.2		c.665-12_665-10delTCT		intron	N/A	NP_001306599.1	Q99619-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB2	ENST00000524270.6	TSL:1 MANE Select	c.665-12_665-10delTCT		intron	N/A	ENSP00000428338.1	Q99619-1
	SPSB2	ENST00000523102.5	TSL:1	c.665-12_665-10delTCT		intron	N/A	ENSP00000430872.1	Q99619-1
	SPSB2	ENST00000890095.1		c.665-12_665-10delTCT		intron	N/A	ENSP00000560154.1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3592 AN: 152214 Hom.: 155 Cov.: 32

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

GnomAD2 exomes AF: 0.00712 AC: 1752 AN: 246126 AF XY: 0.00569

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 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

African (AFR) AF: 0.0833 AC: 2788 AN: 33460

American (AMR) AF: 0.00462 AC: 206 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 441 AN: 25826

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39688

South Asian (SAS) AF: 0.000151 AC: 13 AN: 85864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52684

Middle Eastern (MID) AF: 0.00817 AC: 47 AN: 5750

European-Non Finnish (NFE) AF: 0.000251 AC: 279 AN: 1110446

Other (OTH) AF: 0.00546 AC: 329 AN: 60308

GnomAD4 genome AF: 0.0238 AC: 3619 AN: 152332 Hom.: 161 Cov.: 32 AF XY: 0.0227 AC XY: 1689 AN XY: 74494

African (AFR) AF: 0.0820 AC: 3407 AN: 41560

American (AMR) AF: 0.00686 AC: 105 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68028

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0151 Hom.: 11

Bravo AF: 0.0271

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs143871029; hg19: chr12-6980492;