chr11-14000092-T-C

Variant names:

• chr11-14000092-T-C
• rs2618516
• NM_006108.4:c.345+17139T>C

Variant summary

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

The NM_006108.4(SPON1):​c.345+17139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,062 control chromosomes in the GnomAD database, including 32,472 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 0.65 (32472 hom., cov: 32)
• Consequence: SPON1 NM_006108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPON1	NM_006108.4	c.345+17139T>C		intron_variant	Intron 2 of 15	ENST00000576479.4	NP_006099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4	c.345+17139T>C		intron_variant	Intron 2 of 15	1	NM_006108.4	ENSP00000460236.1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98876 AN: 151944 Hom.: 32414 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.651 AC: 98998 AN: 152062 Hom.: 32472 Cov.: 32 AF XY: 0.650 AC XY: 48269 AN XY: 74312

African (AFR) AF: 0.716 AC: 29720 AN: 41484

American (AMR) AF: 0.700 AC: 10712 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2049 AN: 3466

East Asian (EAS) AF: 0.696 AC: 3598 AN: 5170

South Asian (SAS) AF: 0.494 AC: 2382 AN: 4820

European-Finnish (FIN) AF: 0.642 AC: 6773 AN: 10554

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41691 AN: 67958

Other (OTH) AF: 0.663 AC: 1398 AN: 2110

Alfa AF: 0.623 Hom.: 123100

Bravo AF: 0.661

Asia WGS AF: 0.566 AC: 1968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.1
DANN	Benign	0.63
PhyloP100		-0.44

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: rs2618516; hg19: chr11-14021639;