chr11-14197151-T-C

Position:

• chr11-14197151-T-C

Variant summary

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

The NM_006108.4(SPON1):​c.826-46181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 152,318 control chromosomes in the GnomAD database, including 77 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 0.027 (77 hom., cov: 32)
• Consequence: SPON1 NM_006108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPON1	NM_006108.4	c.826-46181T>C		intron_variant		ENST00000576479.4	NP_006099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4	c.826-46181T>C		intron_variant		1	NM_006108.4	ENSP00000460236.1

Frequencies

GnomAD3 genomes AF: 0.0267 AC: 4065 AN: 152200 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0267 AC: 4062 AN: 152318 Hom.: 77 Cov.: 32 AF XY: 0.0291 AC XY: 2164 AN XY: 74484

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0940

Gnomad4 FIN AF: 0.0489

Gnomad4 NFE AF: 0.0249

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0235 Hom.: 82

Bravo AF: 0.0224

Asia WGS AF: 0.0650 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.77

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: rs11606345; hg19: chr11-14218697;