11-14266582-G-T

Variant names:

• chr11-14266582-G-T
• rs11238
• NM_006108.4:c.*895G>T

Variant summary

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

The NM_006108.4(SPON1):​c.*895G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,822 control chromosomes in the GnomAD database, including 6,315 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 0.27 (6315 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SPON1 NM_006108.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 8 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]

SPON1-AS1 (HGNC:53117): (SPON1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPON1	NM_006108.4	c.*895G>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000576479.4	NP_006099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4	c.*895G>T		3_prime_UTR_variant	Exon 16 of 16	1	NM_006108.4	ENSP00000460236.1
SPON1-AS1	ENST00000534587.1	n.39-3535C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41186 AN: 151704 Hom.: 6313 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.267

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.271 AC: 41211 AN: 151822 Hom.: 6315 Cov.: 31 AF XY: 0.278 AC XY: 20627 AN XY: 74170

African (AFR) AF: 0.118 AC: 4891 AN: 41428

American (AMR) AF: 0.261 AC: 3990 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2101 AN: 5150

South Asian (SAS) AF: 0.370 AC: 1775 AN: 4796

European-Finnish (FIN) AF: 0.383 AC: 4014 AN: 10488

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.326 AC: 22136 AN: 67922

Other (OTH) AF: 0.270 AC: 567 AN: 2102

Alfa AF: 0.269 Hom.: 2698

Bravo AF: 0.255

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.13

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: rs11238; hg19: chr11-14288128;