rs6532040

Variant names:

• chr4-87981050-A-G
• rs6532040
• NM_001040058.2:c.217-425A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-87981050-A-G
• chr4-87981050-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040058.2(SPP1):​c.217-425A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,032 control chromosomes in the GnomAD database, including 7,903 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 0.31 (7903 hom., cov: 32)
• Consequence: SPP1 NM_001040058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286618 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.217-425A>G		intron_variant	Intron 5 of 6	ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8	c.217-425A>G		intron_variant	Intron 5 of 6	1	NM_001040058.2	ENSP00000378517.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47526 AN: 151914 Hom.: 7901 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0448

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.313 AC: 47549 AN: 152032 Hom.: 7903 Cov.: 32 AF XY: 0.311 AC XY: 23082 AN XY: 74296

African (AFR) AF: 0.406 AC: 16829 AN: 41456

American (AMR) AF: 0.222 AC: 3396 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3468

East Asian (EAS) AF: 0.0451 AC: 234 AN: 5184

South Asian (SAS) AF: 0.379 AC: 1827 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2843 AN: 10568

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20269 AN: 67936

Other (OTH) AF: 0.270 AC: 570 AN: 2112

Alfa AF: 0.304 Hom.: 929

Bravo AF: 0.313

Asia WGS AF: 0.220 AC: 761 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.34
DANN	Benign	0.47
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6532040; hg19: chr4-88902202;