chr11-14202800-G-A

Variant names:

• chr11-14202800-G-A
• rs11023139
• NM_006108.4:c.826-40532G>A

Variant summary

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

The NM_006108.4(SPON1):​c.826-40532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 152,042 control chromosomes in the GnomAD database, including 379 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 0.062 (379 hom., cov: 32)
• Consequence: SPON1 NM_006108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 19 publications found

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPON1	NM_006108.4	c.826-40532G>A		intron_variant	Intron 6 of 15	ENST00000576479.4	NP_006099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4	c.826-40532G>A		intron_variant	Intron 6 of 15	1	NM_006108.4	ENSP00000460236.1

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9490 AN: 151924 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00852

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0465

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

GnomAD4 genome AF: 0.0625 AC: 9501 AN: 152042 Hom.: 379 Cov.: 32 AF XY: 0.0596 AC XY: 4429 AN XY: 74326

African (AFR) AF: 0.106 AC: 4400 AN: 41462

American (AMR) AF: 0.0352 AC: 538 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.00832 AC: 40 AN: 4806

European-Finnish (FIN) AF: 0.0692 AC: 729 AN: 10540

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0527 AC: 3584 AN: 68000

Other (OTH) AF: 0.0460 AC: 97 AN: 2108

Alfa AF: 0.0544 Hom.: 486

Bravo AF: 0.0617

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		-0.20

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

Other links and lift over

dbSNP: rs11023139; hg19: chr11-14224346;