chr4-87977789-C-T

Variant names:

• chr4-87977789-C-T
• rs11728697
• NM_001040058.2:c.93+692C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM1 BP4_Strong BA1

The NM_001251830.2(SPP1):​c.71C>T​(p.Ala24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,279,012 control chromosomes in the GnomAD database, including 206,942 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (18285 hom., cov: 32)
  • Exomes 𝑓: 0.57 (188657 hom.)
• Consequence: SPP1 NM_001251830.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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]

ENSG00000286618 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity OSTP_HUMAN
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2	c.93+692C>T		intron_variant	Intron 3 of 6	ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8	c.93+692C>T		intron_variant	Intron 3 of 6	1	NM_001040058.2	ENSP00000378517.3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70577 AN: 151908 Hom.: 18290 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.513

GnomAD3 exomes AF: 0.539 AC: 65103 AN: 120696 Hom.: 18531 AF XY: 0.551 AC XY: 36501 AN XY: 66270

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.526

Gnomad ASJ exome AF: 0.630

Gnomad EAS exome AF: 0.346

Gnomad SAS exome AF: 0.637

Gnomad FIN exome AF: 0.512

Gnomad NFE exome AF: 0.577

Gnomad OTH exome AF: 0.542

GnomAD4 exome AF: 0.573 AC: 646128 AN: 1126986 Hom.: 188657 Cov.: 34 AF XY: 0.578 AC XY: 319117 AN XY: 552514

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.646

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.464 AC: 70594 AN: 152026 Hom.: 18285 Cov.: 32 AF XY: 0.462 AC XY: 34327 AN XY: 74290

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.512

Alfa AF: 0.532 Hom.: 11630

Bravo AF: 0.452

Asia WGS AF: 0.508 AC: 1768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11728697; hg19: chr4-88898941; COSMIC: COSV52951541;