rs6839524

Positions:

• chr4-87978381-C-G
• chr4-87978381-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.93+1284C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 147,564 control chromosomes in the GnomAD database, including 3,834 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 (3834 hom., cov: 30)
• Consequence: SPP1 NM_001040058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPP1	NM_001040058.2	c.93+1284C>G		intron_variant		ENST00000395080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPP1	ENST00000395080.8	c.93+1284C>G		intron_variant		1	NM_001040058.2	P1
	ENST00000662475.1	n.308-2519G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.173 AC: 25537 AN: 147508 Hom.: 3831 Cov.: 30

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.173 AC: 25557 AN: 147564 Hom.: 3834 Cov.: 30 AF XY: 0.177 AC XY: 12672 AN XY: 71722

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0587

Gnomad4 OTH AF: 0.163

Alfa AF: 0.116 Hom.: 268

Bravo AF: 0.190

Asia WGS AF: 0.265 AC: 919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.24

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: rs6839524; hg19: chr4-88899533;