Variant rs7435825 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000395080.8(SPP1):c.671G>A(p.Ser224Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00824 in 1,614,054 control chromosomes in the GnomAD database, including 918 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.043 ( 488 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 430 hom. )

Consequence

SPP1
ENST00000395080.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001668185).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPP1	NM_001040058.2 linkuse as main transcript	c.671G>A	p.Ser224Asn	missense_variant	7/7	ENST00000395080.8	NP_001035147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8 linkuse as main transcript	c.671G>A	p.Ser224Asn	missense_variant	7/7	1	NM_001040058.2	ENSP00000378517	P1	P10451-1
	ENST00000662475.1 linkuse as main transcript	n.307+6736C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0434

AC:

6597

AN:

152046

Hom.:

489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0153

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0116

AC:

2910

AN:

251480

Hom.:

189

AF XY:

0.00834

AC XY:

1133

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.00789

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00537

GnomAD4 exome

AF:

0.00458

AC:

6689

AN:

1461890

Hom.:

430

Cov.:

AF XY:

0.00396

AC XY:

2883

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.00928

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.0434

AC:

6608

AN:

152164

Hom.:

488

Cov.:

AF XY:

0.0421

AC XY:

3134

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0152

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.00853

Hom.:

155

Bravo

AF:

0.0497

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.143

AC:

628

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0143

AC:

1740

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.42

.;.;T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.64

T;T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;.;M;.;.

MutationTaster

Benign

0.55

P;P;P

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.6

.;D;D;N;D

REVEL

Benign

0.087

Sift

Uncertain

0.014

.;D;D;D;D

Sift4G

Uncertain

0.0060

D;T;D;D;T

Polyphen

0.59

.;.;P;.;.

Vest4

0.049

MPC

0.11

ClinPred

0.041

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over