rs1025412

Positions:

• chr11-14224750-G-A
• chr11-14224750-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006108.4(SPON1):​c.826-18582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 499,704 control chromosomes in the GnomAD database, including 67,987 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 0.51 (20326 hom., cov: 31)
  • Exomes 𝑓: 0.52 (47661 hom.)
• Consequence: SPON1 NM_006108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPON1	NM_006108.4	c.826-18582G>A		intron_variant		ENST00000576479.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPON1	ENST00000576479.4	c.826-18582G>A		intron_variant		1	NM_006108.4	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78114 AN: 151886 Hom.: 20324 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.510 AC: 110327 AN: 216250 Hom.: 28952 AF XY: 0.518 AC XY: 61845 AN XY: 119284

Gnomad AFR exome AF: 0.501

Gnomad AMR exome AF: 0.395

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.621

Gnomad SAS exome AF: 0.575

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.524

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.517 AC: 179595 AN: 347700 Hom.: 47661 Cov.: 0 AF XY: 0.526 AC XY: 104959 AN XY: 199450

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.396

Gnomad4 ASJ exome AF: 0.405

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.575

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.514 AC: 78153 AN: 152004 Hom.: 20326 Cov.: 31 AF XY: 0.515 AC XY: 38260 AN XY: 74284

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.498

Alfa AF: 0.523 Hom.: 48643

Bravo AF: 0.511

Asia WGS AF: 0.544 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.54
DANN	Benign	0.67

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: rs1025412; hg19: chr11-14246296; COSMIC: COSV59958291;