4-87981253-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	UniProt
SPP1	NM_001040058.2	c.217-222C>T		intron_variant		ENST00000395080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPP1	ENST00000395080.8	c.217-222C>T		intron_variant		1	NM_001040058.2	P1
	ENST00000662475.1	n.308-5391G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.0453

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.271

Alfa AF: 0.284 Hom.: 5833

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

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: rs6811536; hg19: chr4-88902405;