Genetic Variant NM_006108.4: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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006108.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPON1	NM_006108.4	MANE Select	c.826-18582G>A		intron	N/A	NP_006099.2	Q9HCB6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPON1	ENST00000576479.4	TSL:1 MANE Select	c.826-18582G>A	intron	N/A	ENSP00000460236.1	Q9HCB6
SPON1	ENST00000964987.1		c.826-18582G>A	intron	N/A	ENSP00000635046.1
SPON1	ENST00000883678.1		c.826-18582G>A	intron	N/A	ENSP00000553737.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over