4-87981253-C-T

Variant names:

• chr4-87981253-C-T
• rs6811536
• NM_001040058.2:c.217-222C>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.217-222C>T 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 151,978 control chromosomes in the GnomAD database, including 7,913 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 (7913 hom., cov: 32)
• Consequence: SPP1 NM_001040058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.217-222C>T		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.217-222C>T		intron_variant	Intron 5 of 6	1	NM_001040058.2	ENSP00000378517.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47560 AN: 151862 Hom.: 7911 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.313 AC: 47583 AN: 151978 Hom.: 7913 Cov.: 32 AF XY: 0.311 AC XY: 23119 AN XY: 74282

African (AFR) AF: 0.407 AC: 16851 AN: 41422

American (AMR) AF: 0.222 AC: 3398 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3470

East Asian (EAS) AF: 0.0453 AC: 235 AN: 5182

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

European-Finnish (FIN) AF: 0.270 AC: 2841 AN: 10526

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

European-Non Finnish (NFE) AF: 0.298 AC: 20277 AN: 67964

Other (OTH) AF: 0.271 AC: 571 AN: 2110

Alfa AF: 0.287 Hom.: 7177

Bravo AF: 0.313

Asia WGS AF: 0.220 AC: 765 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.62
PhyloP100		0.20
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: rs6811536; hg19: chr4-88902405;