rs1126772

chr4-87983034-A-G

Variant summary

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

The NM_001040058.2(SPP1):c.*138A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 884,880 control chromosomes in the GnomAD database, including 18,996 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 0.17 (2553 hom., cov: 32)
  • Exomes 𝑓: 0.20 (16443 hom.)
• Consequence: SPP1 NM_001040058.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPP1	NM_001040058.2	c.*138A>G		3_prime_UTR_variant	7/7	ENST00000395080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPP1	ENST00000395080.8	c.*138A>G		3_prime_UTR_variant	7/7	1	NM_001040058.2	P1
	ENST00000662475.1	n.307+6324T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25264 AN: 152084 Hom.: 2550 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.204 AC: 149256 AN: 732678 Hom.: 16443 Cov.: 10 AF XY: 0.204 AC XY: 75525 AN XY: 370814

Gnomad4 AFR exome AF: 0.0433

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.166 AC: 25271 AN: 152202 Hom.: 2553 Cov.: 32 AF XY: 0.162 AC XY: 12065 AN XY: 74418

Gnomad4 AFR AF: 0.0509

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.212

Alfa AF: 0.212 Hom.: 3625

Bravo AF: 0.167

Asia WGS AF: 0.205 AC: 715 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.6
Dann	Benign	0.57
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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: rs1126772; hg19: chr4-88904186; COSMIC: COSV52952449; COSMIC: COSV52952449;