11-13963036-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_006108.4(SPON1):c.132C>T(p.Cys44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,586,008 control chromosomes in the GnomAD database, including 55,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4675 hom., cov: 34)
  • Exomes 𝑓: 0.26 (51318 hom.)
• Consequence: SPON1 NM_006108.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

Genes affected

SPON1 (HGNC:11252): (spondin 1) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in cell adhesion. Predicted to act upstream of or within positive regulation of protein binding activity; positive regulation of protein processing; and regulation of amyloid precursor protein catabolic process. Located in extracellular space. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 11-13963036-C-T is Benign according to our data. Variant chr11-13963036-C-T is described in ClinVar as [Benign]. Clinvar id is 1179535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPON1	NM_006108.4	c.132C>T	p.Cys44=	synonymous_variant	1/16	ENST00000576479.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPON1	ENST00000576479.4	c.132C>T	p.Cys44=	synonymous_variant	1/16	1	NM_006108.4	P1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37046 AN: 152108 Hom.: 4674 Cov.: 34

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.273

GnomAD3 exomes AF: 0.244 AC: 48068 AN: 196850 Hom.: 6374 AF XY: 0.257 AC XY: 27843 AN XY: 108162

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.155

Gnomad SAS exome AF: 0.358

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.263 AC: 377200 AN: 1433784 Hom.: 51318 Cov.: 36 AF XY: 0.266 AC XY: 189142 AN XY: 710896

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.243 AC: 37053 AN: 152224 Hom.: 4675 Cov.: 34 AF XY: 0.240 AC XY: 17899 AN XY: 74426

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.272

Alfa AF: 0.268 Hom.: 1988

Bravo AF: 0.239

Asia WGS AF: 0.234 AC: 815 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	16
Dann	Benign	0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs3761859; hg19: chr11-13984583; COSMIC: COSV59963790;