dbSNP rs9138: SPP1:n.1528A>C (chr4-87983190-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000509659.5(SPP1):n.1528A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 233,210 control chromosomes in the GnomAD database, including 10,451 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 ( 6164 hom., cov: 33)

Exomes 𝑓: 0.31 ( 4287 hom. )

Consequence

SPP1
ENST00000509659.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.442

Publications

74 publications found

Variant links:

Genes affected

SPP1 (HGNC:11255): (secreted phosphoprotein 1) The protein encoded by this gene is involved in the attachment of osteoclasts to the mineralized bone matrix. The encoded protein is secreted and binds hydroxyapatite with high affinity. The osteoclast vitronectin receptor is found in the cell membrane and may be involved in the binding to this protein. This protein is also a cytokine that upregulates expression of interferon-gamma and interleukin-12. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SPP1 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

SPP1 links:

ENSG00000286618 (HGNC:):

ENSG00000286618 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2 link	c.*294A>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000395080.8	NP_001035147.1	P10451-1A0A024RDE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8 link	c.*294A>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001040058.2	ENSP00000378517.3		P10451-1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40861

AN:

152060

Hom.:

6165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.692

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.305

AC:

24715

AN:

81032

Hom.:

4287

Cov.:

AF XY:

0.305

AC XY:

12567

AN XY:

41168

show subpopulations

African (AFR)

AF:

0.180

AC:

449

AN:

2500

American (AMR)

AF:

0.354

AC:

1447

AN:

4082

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

916

AN:

3044

East Asian (EAS)

AF:

0.662

AC:

3934

AN:

5946

South Asian (SAS)

AF:

0.325

AC:

1383

AN:

4256

European-Finnish (FIN)

AF:

0.291

AC:

989

AN:

3396

Middle Eastern (MID)

AF:

0.376

AC:

146

AN:

388

European-Non Finnish (NFE)

AF:

0.265

AC:

13819

AN:

52158

Other (OTH)

AF:

0.310

AC:

1632

AN:

5262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

838

1676

2514

3352

4190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

296

444

592

740

<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:

0.269

AC:

40890

AN:

152178

Hom.:

6164

Cov.:

AF XY:

0.271

AC XY:

20178

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.176

AC:

7290

AN:

41504

American (AMR)

AF:

0.327

AC:

5004

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1095

AN:

3468

East Asian (EAS)

AF:

0.692

AC:

3583

AN:

5178

South Asian (SAS)

AF:

0.341

AC:

1643

AN:

4820

European-Finnish (FIN)

AF:

0.289

AC:

3064

AN:

10602

Middle Eastern (MID)

AF:

0.411

AC:

120

AN:

292

European-Non Finnish (NFE)

AF:

0.268

AC:

18216

AN:

67996

Other (OTH)

AF:

0.333

AC:

703

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1502

3004

4505

6007

7509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.225

Hom.:

1343

Bravo

AF:

0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.6

(source)

DANN

Benign

0.86

PhyloP100

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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