rs2853749

Positions:

• chr4-87976662-C-T

Variant summary

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

The NM_001040058.2(SPP1):​c.-14-220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,926 control chromosomes in the GnomAD database, including 8,707 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 0.33 (8707 hom., cov: 32)
• Consequence: SPP1 NM_001040058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.-14-220C>T		intron_variant		ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8	c.-14-220C>T		intron_variant		1	NM_001040058.2	ENSP00000378517.3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50550 AN: 151810 Hom.: 8699 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.333 AC: 50586 AN: 151926 Hom.: 8707 Cov.: 32 AF XY: 0.334 AC XY: 24789 AN XY: 74224

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.327

Alfa AF: 0.324 Hom.: 1066

Bravo AF: 0.328

Asia WGS AF: 0.297 AC: 1025 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.16

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: rs2853749; hg19: chr4-88897814;