dbSNP rs17013181: IBSP:p.Arg219Gly (chr4-87811611-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004967.4(IBSP):c.655A>G(p.Arg219Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,613,262 control chromosomes in the GnomAD database, including 41,893 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.26 ( 5463 hom., cov: 30)

Exomes 𝑓: 0.22 ( 36430 hom. )

Consequence

IBSP
NM_004967.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.210

Publications

37 publications found

Variant links:

Genes affected

IBSP (HGNC:5341): (integrin binding sialoprotein) The protein encoded by this gene is a major structural protein of the bone matrix. It constitutes approximately 12% of the noncollagenous proteins in human bone and is synthesized by skeletal-associated cell types, including hypertrophic chondrocytes, osteoblasts, osteocytes, and osteoclasts. The only extraskeletal site of its synthesis is the trophoblast. This protein binds to calcium and hydroxyapatite via its acidic amino acid clusters, and mediates cell attachment through an RGD sequence that recognizes the vitronectin receptor. [provided by RefSeq, Jul 2008]

IBSP links:

ENSG00000307815 (HGNC:):

ENSG00000307815 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003080666).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IBSP	NM_004967.4 link	c.655A>G	p.Arg219Gly	missense_variant	Exon 7 of 7	ENST00000226284.7	NP_004958.2	P21815

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IBSP	ENST00000226284.7 link	c.655A>G	p.Arg219Gly	missense_variant	Exon 7 of 7	1	NM_004967.4	ENSP00000226284.5		P21815

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38702

AN:

151620

Hom.:

5455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.239

GnomAD2 exomes

AF:

0.208

AC:

52174

AN:

250694

AF XY:

0.202

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.220

AC:

322026

AN:

1461524

Hom.:

36430

Cov.:

AF XY:

0.217

AC XY:

157853

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.377

AC:

12620

AN:

33468

American (AMR)

AF:

0.230

AC:

10254

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

3073

AN:

26134

East Asian (EAS)

AF:

0.256

AC:

10171

AN:

39674

South Asian (SAS)

AF:

0.154

AC:

13289

AN:

86222

European-Finnish (FIN)

AF:

0.156

AC:

8341

AN:

53400

Middle Eastern (MID)

AF:

0.188

AC:

1084

AN:

5764

European-Non Finnish (NFE)

AF:

0.225

AC:

249823

AN:

1111800

Other (OTH)

AF:

0.221

AC:

13371

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

13568

27136

40704

54272

67840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8760

17520

26280

35040

43800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.255

AC:

38746

AN:

151738

Hom.:

5463

Cov.:

AF XY:

0.250

AC XY:

18505

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.376

AC:

15542

AN:

41314

American (AMR)

AF:

0.256

AC:

3902

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

393

AN:

3464

East Asian (EAS)

AF:

0.213

AC:

1094

AN:

5140

South Asian (SAS)

AF:

0.152

AC:

723

AN:

4768

European-Finnish (FIN)

AF:

0.155

AC:

1637

AN:

10578

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14643

AN:

67906

Other (OTH)

AF:

0.237

AC:

501

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1409

2818

4228

5637

7046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.228

Hom.:

13181

Bravo

AF:

0.270

TwinsUK

AF:

0.223

AC:

827

ALSPAC

AF:

0.229

AC:

884

ESP6500AA

AF:

0.361

AC:

1590

ESP6500EA

AF:

0.220

AC:

1890

ExAC

AF:

0.211

AC:

25572

Asia WGS

AF:

0.227

AC:

792

AN:

3478

EpiCase

AF:

0.213

EpiControl

AF:

0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.7

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.032

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.29

PhyloP100

0.21

PrimateAI

Benign

0.19

PROVEAN

Benign

0.33

REVEL

Benign

0.021

Sift

Benign

0.23

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.010

MPC

0.18

ClinPred

0.0012

GERP RS

3.3

Varity_R

0.059

gMVP

0.32

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over