rs6812524

Variant names:

• chr4-87981573-G-A
• rs6812524
• NM_001040058.2:c.315G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-87981573-G-A
• chr4-87981573-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001040058.2(SPP1):​c.315G>A​(p.Ser105Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,576 control chromosomes in the GnomAD database, including 1,816 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 0.062 (947 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (869 hom.)
• Consequence: SPP1 NM_001040058.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• Publications: 5 publications found

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

ENSG00000286618 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-3.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040058.2. 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
	SPP1	NM_001040058.2	MANE Select	c.315G>A	p.Ser105Ser	synonymous	Exon 6 of 7	NP_001035147.1	P10451-1
	SPP1	NM_001251830.2		c.354G>A	p.Ser118Ser	synonymous	Exon 7 of 8	NP_001238759.1	B7Z351
	SPP1	NM_000582.3		c.273G>A	p.Ser91Ser	synonymous	Exon 5 of 6	NP_000573.1	P10451-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPP1	ENST00000395080.8	TSL:1 MANE Select	c.315G>A	p.Ser105Ser	synonymous	Exon 6 of 7	ENSP00000378517.3	P10451-1
	SPP1	ENST00000237623.11	TSL:1	c.273G>A	p.Ser91Ser	synonymous	Exon 5 of 6	ENSP00000237623.7	P10451-5
	SPP1	ENST00000360804.4	TSL:1	c.234G>A	p.Ser78Ser	synonymous	Exon 5 of 6	ENSP00000354042.4	P10451-3

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9324 AN: 151950 Hom.: 942 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0468

GnomAD2 exomes AF: 0.0165 AC: 4146 AN: 251474 AF XY: 0.0121

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000782

Gnomad OTH exome AF: 0.00961

GnomAD4 exome AF: 0.00666 AC: 9727 AN: 1461508 Hom.: 869 Cov.: 32 AF XY: 0.00578 AC XY: 4201 AN XY: 727074

African (AFR) AF: 0.222 AC: 7420 AN: 33466

American (AMR) AF: 0.0139 AC: 622 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000880 AC: 23 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000673 AC: 58 AN: 86236

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53324

Middle Eastern (MID) AF: 0.0158 AC: 91 AN: 5766

European-Non Finnish (NFE) AF: 0.000544 AC: 605 AN: 1111784

Other (OTH) AF: 0.0150 AC: 904 AN: 60376

GnomAD4 genome AF: 0.0615 AC: 9356 AN: 152068 Hom.: 947 Cov.: 32 AF XY: 0.0593 AC XY: 4412 AN XY: 74366

African (AFR) AF: 0.213 AC: 8806 AN: 41430

American (AMR) AF: 0.0246 AC: 377 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 67998

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0285 Hom.: 293

Bravo AF: 0.0699

Asia WGS AF: 0.0150 AC: 52 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.43
DANN	Benign	0.42
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6812524; hg19: chr4-88902725;