dbSNP rs1025412: SPON1:c.826-18582G>A (chr11-14224750-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006108.4(SPON1):c.826-18582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 499,704 control chromosomes in the GnomAD database, including 67,987 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 0.51 ( 20326 hom., cov: 31)

Exomes 𝑓: 0.52 ( 47661 hom. )

Consequence

SPON1
NM_006108.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.635

Publications

15 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPON1	NM_006108.4 link	c.826-18582G>A		intron_variant	Intron 6 of 15	ENST00000576479.4	NP_006099.2	Q9HCB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4 link	c.826-18582G>A		intron_variant	Intron 6 of 15	1	NM_006108.4	ENSP00000460236.1		Q9HCB6

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78114

AN:

151886

Hom.:

20324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.786

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.493

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.529

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.510

AC:

110327

AN:

216250

AF XY:

0.518

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.621

Gnomad FIN exome

AF:

0.488

Gnomad NFE exome

AF:

0.524

Gnomad OTH exome

AF:

0.498

GnomAD4 exome

AF:

0.517

AC:

179595

AN:

347700

Hom.:

47661

Cov.:

AF XY:

0.526

AC XY:

104959

AN XY:

199450

show subpopulations

African (AFR)

AF:

0.499

AC:

4982

AN:

9988

American (AMR)

AF:

0.396

AC:

13702

AN:

34644

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

4489

AN:

11092

East Asian (EAS)

AF:

0.621

AC:

7879

AN:

12694

South Asian (SAS)

AF:

0.575

AC:

35622

AN:

61982

European-Finnish (FIN)

AF:

0.494

AC:

8075

AN:

16338

Middle Eastern (MID)

AF:

0.439

AC:

1223

AN:

2786

European-Non Finnish (NFE)

AF:

0.524

AC:

95526

AN:

182438

Other (OTH)

AF:

0.514

AC:

8097

AN:

15738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

3274

6548

9822

13096

16370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

752

1504

2256

3008

3760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.514

AC:

78153

AN:

152004

Hom.:

20326

Cov.:

AF XY:

0.515

AC XY:

38260

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.501

AC:

20754

AN:

41438

American (AMR)

AF:

0.444

AC:

6785

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1443

AN:

3468

East Asian (EAS)

AF:

0.632

AC:

3262

AN:

5158

South Asian (SAS)

AF:

0.590

AC:

2844

AN:

4818

European-Finnish (FIN)

AF:

0.493

AC:

5201

AN:

10560

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.529

AC:

35962

AN:

67964

Other (OTH)

AF:

0.498

AC:

1053

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1899

3798

5698

7597

9496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.523

Hom.:

99171

Bravo

AF:

0.511

Asia WGS

AF:

0.544

AC:

1891

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.54

(source)

DANN

Benign

0.67

PhyloP100

-0.64

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over