Genetic Variant ENST00000509659.5:n.1372A>G (chr4-87983034-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000509659.5(SPP1):n.1372A>G 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 0.197 in 884,880 control chromosomes in the GnomAD database, including 18,996 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 0.17 ( 2553 hom., cov: 32)

Exomes 𝑓: 0.20 ( 16443 hom. )

Consequence

SPP1
ENST00000509659.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.193

Publications

59 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:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2 link	c.*138A>G		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.*138A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001040058.2	ENSP00000378517.3		P10451-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25264

AN:

152084

Hom.:

2550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0509

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.212

GnomAD4 exome

AF:

0.204

AC:

149256

AN:

732678

Hom.:

16443

Cov.:

AF XY:

0.204

AC XY:

75525

AN XY:

370814

show subpopulations

African (AFR)

AF:

0.0433

AC:

763

AN:

17622

American (AMR)

AF:

0.205

AC:

3604

AN:

17578

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

4053

AN:

15366

East Asian (EAS)

AF:

0.320

AC:

10207

AN:

31922

South Asian (SAS)

AF:

0.174

AC:

8436

AN:

48516

European-Finnish (FIN)

AF:

0.136

AC:

4135

AN:

30306

Middle Eastern (MID)

AF:

0.300

AC:

770

AN:

2570

European-Non Finnish (NFE)

AF:

0.206

AC:

109959

AN:

533586

Other (OTH)

AF:

0.208

AC:

7329

AN:

35212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5671

11342

17013

22684

28355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2776

5552

8328

11104

13880

<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:

0.166

AC:

25271

AN:

152202

Hom.:

2553

Cov.:

AF XY:

0.162

AC XY:

12065

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0509

AC:

2114

AN:

41554

American (AMR)

AF:

0.206

AC:

3153

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

941

AN:

3472

East Asian (EAS)

AF:

0.279

AC:

1443

AN:

5174

South Asian (SAS)

AF:

0.172

AC:

829

AN:

4814

European-Finnish (FIN)

AF:

0.135

AC:

1433

AN:

10598

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14685

AN:

67978

Other (OTH)

AF:

0.212

AC:

448

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1051

2102

3152

4203

5254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.210

Hom.:

4200

Bravo

AF:

0.167

Asia WGS

AF:

0.205

AC:

715

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

(source)

DANN

Benign

0.57

PhyloP100

-0.19

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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