rs17556665

Positions:

• chr11-14076935-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPON1	NM_006108.4	c.553+1517G>T		intron_variant		ENST00000576479.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPON1	ENST00000576479.4	c.553+1517G>T		intron_variant		1	NM_006108.4	P1

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

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0932

Gnomad4 ASJ AF: 0.0946

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.0434

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0896

Alfa AF: 0.0994 Hom.: 842

Bravo AF: 0.0756

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs17556665; hg19: chr11-14098482;