rs10516799

Positions:

• chr4-87982041-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040058.2(SPP1):​c.540+243C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,704 control chromosomes in the GnomAD database, including 6,665 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 0.29 (6665 hom., cov: 31)
• Consequence: SPP1 NM_001040058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.540+243C>G		intron_variant		ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8	c.540+243C>G		intron_variant		1	NM_001040058.2	ENSP00000378517	P1
	ENST00000662475.1	n.308-6179G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43983 AN: 151586 Hom.: 6663 Cov.: 31

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.290 AC: 44002 AN: 151704 Hom.: 6665 Cov.: 31 AF XY: 0.289 AC XY: 21398 AN XY: 74136

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.0448

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.255

Alfa AF: 0.298 Hom.: 860

Bravo AF: 0.286

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.64

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: rs10516799; hg19: chr4-88903193;