rs7955859

Variant names:

• chr12-26186798-C-T
• rs7955859
• ENST00000540266.5:c.-30-37495C>T

Variant summary

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

The ENST00000540266.5(SSPN):​c.-30-37495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,078 control chromosomes in the GnomAD database, including 6,168 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 0.28 (6168 hom., cov: 32)
• Consequence: SSPN ENST00000540266.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000540266.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSPN	ENST00000540266.5	TSL:4	c.-30-37495C>T		intron	N/A	ENSP00000442893.1
	SSPN	ENST00000538142.5	TSL:4	c.-30-37495C>T		intron	N/A	ENSP00000445360.1
	SSPN	ENST00000534829.5	TSL:3	n.101+64646C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43014 AN: 151960 Hom.: 6166 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.283 AC: 43038 AN: 152078 Hom.: 6168 Cov.: 32 AF XY: 0.285 AC XY: 21214 AN XY: 74324

African (AFR) AF: 0.294 AC: 12202 AN: 41500

American (AMR) AF: 0.197 AC: 3017 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 896 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1812 AN: 5160

South Asian (SAS) AF: 0.320 AC: 1541 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3659 AN: 10562

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.277 AC: 18806 AN: 67980

Other (OTH) AF: 0.248 AC: 523 AN: 2108

Alfa AF: 0.267 Hom.: 1044

Bravo AF: 0.273

Asia WGS AF: 0.344 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98
DANN	Benign	0.32
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7955859; hg19: chr12-26339731;