NM_001040058.2:c.540+243C>G

Variant names:

• chr4-87982041-C-G
• rs10516799
• NM_001040058.2:c.540+243C>G

Variant summary

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

The NM_001040058.2(SPP1):​c.540+243C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,704 control chromosomes in the GnomAD database, including 6,665 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 0.29 (6665 hom., cov: 31)
• Consequence: SPP1 NM_001040058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.540+243C>G		intron_variant	Intron 6 of 6	ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8	c.540+243C>G		intron_variant	Intron 6 of 6	1	NM_001040058.2	ENSP00000378517.3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43983 AN: 151586 Hom.: 6663 Cov.: 31

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.290 AC: 44002 AN: 151704 Hom.: 6665 Cov.: 31 AF XY: 0.289 AC XY: 21398 AN XY: 74136

African (AFR) AF: 0.327 AC: 13530 AN: 41354

American (AMR) AF: 0.213 AC: 3257 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1115 AN: 3462

East Asian (EAS) AF: 0.0448 AC: 231 AN: 5152

South Asian (SAS) AF: 0.376 AC: 1813 AN: 4816

European-Finnish (FIN) AF: 0.270 AC: 2829 AN: 10478

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20228 AN: 67876

Other (OTH) AF: 0.255 AC: 536 AN: 2100

Alfa AF: 0.298 Hom.: 860

Bravo AF: 0.286

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.64
PhyloP100		-1.1
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: rs10516799; hg19: chr4-88903193;