rs1819084

Variant names:

• chr11-13974608-C-A
• rs1819084
• NM_006108.4:c.239-8239C>A

Variant summary

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

The NM_006108.4(SPON1):​c.239-8239C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,084 control chromosomes in the GnomAD database, including 4,684 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 0.23 (4684 hom., cov: 32)
• Consequence: SPON1 NM_006108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPON1	NM_006108.4	c.239-8239C>A		intron_variant	Intron 1 of 15	ENST00000576479.4	NP_006099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4	c.239-8239C>A		intron_variant	Intron 1 of 15	1	NM_006108.4	ENSP00000460236.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35304 AN: 151966 Hom.: 4677 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.232 AC: 35333 AN: 152084 Hom.: 4684 Cov.: 32 AF XY: 0.238 AC XY: 17680 AN XY: 74322

African (AFR) AF: 0.110 AC: 4544 AN: 41494

American (AMR) AF: 0.282 AC: 4305 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2295 AN: 5174

South Asian (SAS) AF: 0.249 AC: 1200 AN: 4826

European-Finnish (FIN) AF: 0.338 AC: 3570 AN: 10562

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17619 AN: 67958

Other (OTH) AF: 0.243 AC: 512 AN: 2110

Alfa AF: 0.244 Hom.: 6716

Bravo AF: 0.223

Asia WGS AF: 0.325 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.78
PhyloP100		-0.23

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: rs1819084; hg19: chr11-13996155;