NM_001040058.2:c.*138A>G

Variant names:

• chr4-87983034-A-G
• rs1126772
• NM_001040058.2:c.*138A>G

Variant summary

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

The NM_001040058.2(SPP1):​c.*138A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 884,880 control chromosomes in the GnomAD database, including 18,996 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 (2553 hom., cov: 32)
  • Exomes 𝑓: 0.20 (16443 hom.)
• Consequence: SPP1 NM_001040058.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 59 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040058.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPP1	NM_001040058.2	MANE Select	c.*138A>G		3_prime_UTR	Exon 7 of 7	NP_001035147.1	P10451-1
	SPP1	NM_001251830.2		c.*138A>G		3_prime_UTR	Exon 8 of 8	NP_001238759.1	B7Z351
	SPP1	NM_000582.3		c.*138A>G		3_prime_UTR	Exon 6 of 6	NP_000573.1	P10451-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPP1	ENST00000395080.8	TSL:1 MANE Select	c.*138A>G		3_prime_UTR	Exon 7 of 7	ENSP00000378517.3	P10451-1
	SPP1	ENST00000237623.11	TSL:1	c.*138A>G		3_prime_UTR	Exon 6 of 6	ENSP00000237623.7	P10451-5
	SPP1	ENST00000360804.4	TSL:1	c.*138A>G		3_prime_UTR	Exon 6 of 6	ENSP00000354042.4	P10451-3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25264 AN: 152084 Hom.: 2550 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.204 AC: 149256 AN: 732678 Hom.: 16443 Cov.: 10 AF XY: 0.204 AC XY: 75525 AN XY: 370814

African (AFR) AF: 0.0433 AC: 763 AN: 17622

American (AMR) AF: 0.205 AC: 3604 AN: 17578

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 4053 AN: 15366

East Asian (EAS) AF: 0.320 AC: 10207 AN: 31922

South Asian (SAS) AF: 0.174 AC: 8436 AN: 48516

European-Finnish (FIN) AF: 0.136 AC: 4135 AN: 30306

Middle Eastern (MID) AF: 0.300 AC: 770 AN: 2570

European-Non Finnish (NFE) AF: 0.206 AC: 109959 AN: 533586

Other (OTH) AF: 0.208 AC: 7329 AN: 35212

GnomAD4 genome AF: 0.166 AC: 25271 AN: 152202 Hom.: 2553 Cov.: 32 AF XY: 0.162 AC XY: 12065 AN XY: 74418

African (AFR) AF: 0.0509 AC: 2114 AN: 41554

American (AMR) AF: 0.206 AC: 3153 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1443 AN: 5174

South Asian (SAS) AF: 0.172 AC: 829 AN: 4814

European-Finnish (FIN) AF: 0.135 AC: 1433 AN: 10598

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14685 AN: 67978

Other (OTH) AF: 0.212 AC: 448 AN: 2116

Alfa AF: 0.210 Hom.: 4200

Bravo AF: 0.167

Asia WGS AF: 0.205 AC: 715 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		-0.19
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
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: rs1126772; hg19: chr4-88904186; COSMIC: COSV52952449; COSMIC: COSV52952449;