dbSNP rs28357094: ENSG00000286618:n.525A>C (chr4-87975645-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000662475.1(ENSG00000286618):n.525A>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 0.173 in 159,240 control chromosomes in the GnomAD database, including 2,789 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 ( 2645 hom., cov: 32)

Exomes 𝑓: 0.19 ( 144 hom. )

Consequence

ENSG00000286618
ENST00000662475.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

111 publications found

Variant links:

Genes affected

ENSG00000286618 (HGNC:):

ENSG00000286618 links:

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:

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=-0.57).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000662475.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPP1	NM_001040058.2	MANE Select	c.-170T>G	upstream_gene	N/A	NP_001035147.1	P10451-1
SPP1	NM_001251830.2		c.-320T>G	upstream_gene	N/A	NP_001238759.1	B7Z351
SPP1	NM_000582.3		c.-170T>G	upstream_gene	N/A	NP_000573.1	P10451-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000286618	ENST00000662475.1		n.525A>C	non_coding_transcript_exon	Exon 3 of 3
SPP1	ENST00000395080.8	TSL:1 MANE Select	c.-170T>G	upstream_gene	N/A	ENSP00000378517.3	P10451-1
SPP1	ENST00000237623.11	TSL:1	c.-170T>G	upstream_gene	N/A	ENSP00000237623.7	P10451-5

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26264

AN:

151952

Hom.:

2643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0883

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0981

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.187

AC:

1344

AN:

7170

Hom.:

144

Cov.:

AF XY:

0.193

AC XY:

719

AN XY:

3718

show subpopulations

African (AFR)

AF:

0.0965

AC:

AN:

114

American (AMR)

AF:

0.169

AC:

AN:

130

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

AN:

214

East Asian (EAS)

AF:

0.00

AC:

AN:

916

South Asian (SAS)

AF:

0.0909

AC:

AN:

European-Finnish (FIN)

AF:

0.236

AC:

213

AN:

902

Middle Eastern (MID)

AF:

0.0313

AC:

AN:

European-Non Finnish (NFE)

AF:

0.225

AC:

1001

AN:

4458

Other (OTH)

AF:

0.157

AC:

AN:

338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

100

151

201

251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.173

AC:

26261

AN:

152070

Hom.:

2645

Cov.:

AF XY:

0.169

AC XY:

12588

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0881

AC:

3658

AN:

41506

American (AMR)

AF:

0.160

AC:

2440

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

636

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5172

South Asian (SAS)

AF:

0.0988

AC:

476

AN:

4820

European-Finnish (FIN)

AF:

0.233

AC:

2452

AN:

10536

Middle Eastern (MID)

AF:

0.140

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.235

AC:

15985

AN:

67970

Other (OTH)

AF:

0.173

AC:

364

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1066

2131

3197

4262

5328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.154

Hom.:

577

Bravo

AF:

0.162

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.3

PromoterAI

-0.36

Neutral

(source)

Splicing

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