11-13963036-C-T

Variant names:

• chr11-13963036-C-T
• rs3761859
• NM_006108.4:c.132C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006108.4(SPON1):​c.132C>T​(p.Cys44Cys) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.93
• Publications: 11 publications found

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]

LOC124902637 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 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 VariationId is 1179535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006108.4. 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
	SPON1	NM_006108.4	MANE Select	c.132C>T	p.Cys44Cys	synonymous	Exon 1 of 16	NP_006099.2	Q9HCB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPON1	ENST00000576479.4	TSL:1 MANE Select	c.132C>T	p.Cys44Cys	synonymous	Exon 1 of 16	ENSP00000460236.1	Q9HCB6
	SPON1	ENST00000964987.1		c.132C>T	p.Cys44Cys	synonymous	Exon 1 of 16	ENSP00000635046.1
	SPON1	ENST00000883678.1		c.132C>T	p.Cys44Cys	synonymous	Exon 1 of 15	ENSP00000553737.1

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

GnomAD2 exomes AF: 0.244 AC: 48068 AN: 196850 AF XY: 0.257

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 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

African (AFR) AF: 0.217 AC: 6974 AN: 32170

American (AMR) AF: 0.154 AC: 6366 AN: 41456

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 7061 AN: 25510

East Asian (EAS) AF: 0.126 AC: 4743 AN: 37528

South Asian (SAS) AF: 0.354 AC: 29008 AN: 81842

European-Finnish (FIN) AF: 0.177 AC: 8900 AN: 50366

Middle Eastern (MID) AF: 0.330 AC: 1892 AN: 5730

European-Non Finnish (NFE) AF: 0.270 AC: 296673 AN: 1099822

Other (OTH) AF: 0.263 AC: 15583 AN: 59360

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

African (AFR) AF: 0.219 AC: 9084 AN: 41556

American (AMR) AF: 0.214 AC: 3269 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3464

East Asian (EAS) AF: 0.155 AC: 802 AN: 5158

South Asian (SAS) AF: 0.357 AC: 1724 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10614

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18537 AN: 67990

Other (OTH) AF: 0.272 AC: 575 AN: 2114

Alfa AF: 0.268 Hom.: 1988

Bravo AF: 0.239

Asia WGS AF: 0.234 AC: 815 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.95
PhyloP100		1.9
PromoterAI		-0.035	Neutral

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