rs2291138

Variant names:

• chr12-26210970-A-C
• rs2291138
• NM_005086.5:c.280-13323A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-26210970-A-C
• chr12-26210970-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005086.5(SSPN):​c.280-13323A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,008 control chromosomes in the GnomAD database, including 5,486 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 0.26 (5486 hom., cov: 32)
• Consequence: SSPN NM_005086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 3 publications found

Genes affected

SSPN (HGNC:11322): (sarcospan) This gene encodes a member of the dystrophin-glycoprotein complex (DGC). The DGC spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Two alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Oct 2008]

ITPR2-AS1 (HGNC:56072): (ITPR2 and SSPN antisense RNA 1)

ENSG00000255750 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSPN	NM_005086.5	c.280-13323A>C		intron_variant	Intron 1 of 2	ENST00000242729.7	NP_005077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSPN	ENST00000242729.7	c.280-13323A>C		intron_variant	Intron 1 of 2	1	NM_005086.5	ENSP00000242729.2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39328 AN: 151890 Hom.: 5478 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39359 AN: 152008 Hom.: 5486 Cov.: 32 AF XY: 0.267 AC XY: 19802 AN XY: 74298

African (AFR) AF: 0.229 AC: 9482 AN: 41492

American (AMR) AF: 0.224 AC: 3410 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2635 AN: 5164

South Asian (SAS) AF: 0.504 AC: 2432 AN: 4828

European-Finnish (FIN) AF: 0.295 AC: 3118 AN: 10568

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16086 AN: 67918

Other (OTH) AF: 0.266 AC: 561 AN: 2108

Alfa AF: 0.246 Hom.: 18309

Bravo AF: 0.249

Asia WGS AF: 0.491 AC: 1702 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.76
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291138; hg19: chr12-26363903;