rs2343866

Positions:

• chr12-26162149-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000539019.1(SSPN):​n.68-17847C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,944 control chromosomes in the GnomAD database, including 15,581 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 0.42 (15581 hom., cov: 32)
• Consequence: SSPN ENST00000539019.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSPN	XM_011520853.4	c.-31+39997C>T		intron_variant			XP_011519155.1
SSPN	XM_011520855.2	c.-31+27119C>T		intron_variant			XP_011519157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000671460.1	n.172+1328G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63315 AN: 151824 Hom.: 15577 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.417 AC: 63327 AN: 151944 Hom.: 15581 Cov.: 32 AF XY: 0.415 AC XY: 30827 AN XY: 74272

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.457

Alfa AF: 0.501 Hom.: 12098

Bravo AF: 0.417

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2343866; hg19: chr12-26315082;