rs17556665

Variant names:

• chr11-14076935-G-T
• rs17556665
• NM_006108.4:c.553+1517G>T

Variant summary

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

The NM_006108.4(SPON1):​c.553+1517G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 152,092 control chromosomes in the GnomAD database, including 569 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 0.074 (569 hom., cov: 32)
• Consequence: SPON1 NM_006108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 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.553+1517G>T		intron	N/A	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.553+1517G>T		intron	N/A	ENSP00000460236.1	Q9HCB6
	SPON1	ENST00000964987.1		c.553+1517G>T		intron	N/A	ENSP00000635046.1
	SPON1	ENST00000883678.1		c.553+1517G>T		intron	N/A	ENSP00000553737.1

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11280 AN: 151974 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.0946

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0742 AC: 11282 AN: 152092 Hom.: 569 Cov.: 32 AF XY: 0.0720 AC XY: 5350 AN XY: 74350

African (AFR) AF: 0.0259 AC: 1074 AN: 41486

American (AMR) AF: 0.0932 AC: 1423 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 328 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.0580 AC: 279 AN: 4810

European-Finnish (FIN) AF: 0.0434 AC: 460 AN: 10606

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7426 AN: 67974

Other (OTH) AF: 0.0896 AC: 189 AN: 2110

Alfa AF: 0.0932 Hom.: 1109

Bravo AF: 0.0756

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.52
PhyloP100		-0.58

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: rs17556665; hg19: chr11-14098482;