dbSNP rs11439060: ENSG00000286618:n.614dupC (chr4-87975555-T-TG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000662475.1(ENSG00000286618):n.614dupC 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 0.332 in 154,250 control chromosomes in the GnomAD database, including 8,831 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 8756 hom., cov: 0)

Exomes 𝑓: 0.26 ( 75 hom. )

Consequence

ENSG00000286618
ENST00000662475.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

34 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2 link	c.-260_-259insG		upstream_gene_variant		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.-260_-259insG		upstream_gene_variant		1	NM_001040058.2	ENSP00000378517.3		P10451-1

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50617

AN:

151820

Hom.:

8750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.328

GnomAD4 exome

AF:

0.258

AC:

598

AN:

2314

Hom.:

AF XY:

0.267

AC XY:

327

AN XY:

1224

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AF:

0.261

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.241

AC:

AN:

282

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.289

AC:

AN:

270

Middle Eastern (MID)

AF:

0.286

AC:

AN:

European-Non Finnish (NFE)

AF:

0.254

AC:

371

AN:

1462

Other (OTH)

AF:

0.279

AC:

AN:

122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

109

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:

0.333

AC:

50650

AN:

151936

Hom.:

8756

Cov.:

AF XY:

0.334

AC XY:

24812

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.415

AC:

17201

AN:

41420

American (AMR)

AF:

0.268

AC:

4089

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1005

AN:

3468

East Asian (EAS)

AF:

0.367

AC:

1900

AN:

5178

South Asian (SAS)

AF:

0.252

AC:

1213

AN:

4816

European-Finnish (FIN)

AF:

0.364

AC:

3836

AN:

10528

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20252

AN:

67954

Other (OTH)

AF:

0.328

AC:

691

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1710

3420

5129

6839

8549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.308

Hom.:

621

Asia WGS

AF:

0.295

AC:

1024

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.042

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over