rs28357094

Variant names:

• chr4-87975645-T-G
• rs28357094
• ENST00000662475.1:n.525A>C

Variant summary

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

The ENST00000662475.1(ENSG00000286618):​n.525A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 159,240 control chromosomes in the GnomAD database, including 2,789 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 (2645 hom., cov: 32)
  • Exomes 𝑓: 0.19 (144 hom.)
• Consequence: ENSG00000286618 ENST00000662475.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

Genes affected

ENSG00000286618 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.-170T>G		upstream_gene_variant		ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8	c.-170T>G		upstream_gene_variant		1	NM_001040058.2	ENSP00000378517.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26264 AN: 151952 Hom.: 2643 Cov.: 32

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.187 AC: 1344 AN: 7170 Hom.: 144 Cov.: 0 AF XY: 0.193 AC XY: 719 AN XY: 3718

Gnomad4 AFR exome AF: 0.0965

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0909

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.173 AC: 26261 AN: 152070 Hom.: 2645 Cov.: 32 AF XY: 0.169 AC XY: 12588 AN XY: 74338

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.173

Alfa AF: 0.187 Hom.: 468

Bravo AF: 0.162

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28357094; hg19: chr4-88896797;