11-14203640-A-T

Position:

• chr11-14203640-A-T

Variant summary

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

The NM_006108.4(SPON1):​c.826-39692A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,922 control chromosomes in the GnomAD database, including 19,990 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 (19990 hom., cov: 32)
• Consequence: SPON1 NM_006108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPON1	NM_006108.4	c.826-39692A>T		intron_variant		ENST00000576479.4	NP_006099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4	c.826-39692A>T		intron_variant		1	NM_006108.4	ENSP00000460236	P1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77665 AN: 151802 Hom.: 19967 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.512 AC: 77742 AN: 151922 Hom.: 19990 Cov.: 32 AF XY: 0.513 AC XY: 38107 AN XY: 74262

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.491

Alfa AF: 0.520 Hom.: 2517

Bravo AF: 0.509

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.69

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: rs4756778; hg19: chr11-14225186;