rs9138

Positions:

• chr4-87983190-A-C
• chr4-87983190-A-G
• chr4-87983190-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001040058.2(SPP1):​c.*294A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 233,210 control chromosomes in the GnomAD database, including 10,451 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 0.27 (6164 hom., cov: 33)
  • Exomes 𝑓: 0.31 (4287 hom.)
• Consequence: SPP1 NM_001040058.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.*294A>C		3_prime_UTR_variant	7/7	ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8	c.*294A>C		3_prime_UTR_variant	7/7	1	NM_001040058.2	ENSP00000378517	P1
	ENST00000662475.1	n.307+6168T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40861 AN: 152060 Hom.: 6165 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.305 AC: 24715 AN: 81032 Hom.: 4287 Cov.: 0 AF XY: 0.305 AC XY: 12567 AN XY: 41168

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.662

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.269 AC: 40890 AN: 152178 Hom.: 6164 Cov.: 33 AF XY: 0.271 AC XY: 20178 AN XY: 74398

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.333

Alfa AF: 0.218 Hom.: 1163

Bravo AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.6
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9138; hg19: chr4-88904342;