rs1609339

Positions:

• chr11-14117127-G-A
• chr11-14117127-G-C
• chr11-14117127-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.677-18293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 152,090 control chromosomes in the GnomAD database, including 192 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 0.031 (192 hom., cov: 32)
• Consequence: SPON1 NM_006108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPON1	NM_006108.4	c.677-18293G>A		intron_variant		ENST00000576479.4	NP_006099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4	c.677-18293G>A		intron_variant		1	NM_006108.4	ENSP00000460236	P1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4734 AN: 151972 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00602

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00693

Gnomad OTH AF: 0.0250

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

GnomAD4 genome AF: 0.0313 AC: 4768 AN: 152090 Hom.: 192 Cov.: 32 AF XY: 0.0302 AC XY: 2245 AN XY: 74356

Gnomad4 AFR AF: 0.0938

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00582

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.00693

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.00692 Hom.: 4

Bravo AF: 0.0355

Asia WGS AF: 0.00954 AC: 33 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
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: rs1609339; hg19: chr11-14138673;