4-87977789-C-T

Variant names:

• chr4-87977789-C-T
• rs11728697
• ENST00000509659.5:n.321C>T

Variant summary

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

The ENST00000509659.5(SPP1):​n.321C>T variant causes a non coding transcript exon 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. 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 ENST00000509659.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• Publications: 34 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=-0.66).
• 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

GnomAD2 exomes AF: 0.539 AC: 65103 AN: 120696 AF XY: 0.551

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 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

African (AFR) AF: 0.191 AC: 4622 AN: 24142

American (AMR) AF: 0.534 AC: 14392 AN: 26976

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 9823 AN: 15708

East Asian (EAS) AF: 0.369 AC: 4593 AN: 12440

South Asian (SAS) AF: 0.646 AC: 47961 AN: 74262

European-Finnish (FIN) AF: 0.517 AC: 6412 AN: 12404

Middle Eastern (MID) AF: 0.559 AC: 2437 AN: 4362

European-Non Finnish (NFE) AF: 0.582 AC: 533098 AN: 915608

Other (OTH) AF: 0.555 AC: 22790 AN: 41084

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

African (AFR) AF: 0.215 AC: 8911 AN: 41476

American (AMR) AF: 0.498 AC: 7603 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2167 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1973 AN: 5176

South Asian (SAS) AF: 0.644 AC: 3095 AN: 4808

European-Finnish (FIN) AF: 0.517 AC: 5450 AN: 10538

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39671 AN: 67970

Other (OTH) AF: 0.512 AC: 1079 AN: 2108

Alfa AF: 0.496 Hom.: 17141

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
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11728697; hg19: chr4-88898941; COSMIC: COSV52951541;