rs6812524

Positions:

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

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000395080.8(SPP1):​c.315G>A​(p.Ser105=) 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 ENST00000395080.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.315G>A	p.Ser105=	synonymous_variant	6/7	ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8	c.315G>A	p.Ser105=	synonymous_variant	6/7	1	NM_001040058.2	ENSP00000378517	P1
	ENST00000662475.1	n.308-5711C>T		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.0165 AC: 4146 AN: 251474 Hom.: 378 AF XY: 0.0121 AC XY: 1646 AN XY: 135906

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 SAS exome AF: 0.000425

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

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.000880

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000673

Gnomad4 FIN exome AF: 0.0000563

Gnomad4 NFE exome AF: 0.000544

Gnomad4 OTH exome AF: 0.0150

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

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0286 Hom.: 221

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.43
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs6812524; hg19: chr4-88902725;