Genetic Variant SPON1:c.*895G>T (chr11-14266582-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.130

Variant links:

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 links:

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

SPON1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.*895G>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000576479.4	NP_006099.2	Q9HCB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4 link	c.*895G>T		3_prime_UTR_variant	Exon 16 of 16	1	NM_006108.4	ENSP00000460236.1		Q9HCB6
SPON1-AS1	ENST00000534587.1 link	n.39-3535C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41186

AN:

151704

Hom.:

6313

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.271

AC:

41211

AN:

151822

Hom.:

6315

Cov.:

AF XY:

0.278

AC XY:

20627

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.408

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.383

Gnomad4 NFE

AF:

0.326

Gnomad4 OTH

AF:

0.270

Alfa

AF:

0.266

Hom.:

2183

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over