dbSNP rs2291087: ITGB5:p.Asn477Ser (chr3-124796651-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM1BP4_StrongBA1

The NM_002213.5(ITGB5):c.1430A>G(p.Asn477Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,613,950 control chromosomes in the GnomAD database, including 1,516 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.048 ( 254 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1262 hom. )

Consequence

ITGB5
NM_002213.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

Publications

16 publications found

Variant links:

Genes affected

ITGB5 (HGNC:6160): (integrin subunit beta 5) This gene encodes a beta subunit of integrin, which can combine with different alpha chains to form a variety of integrin heterodimers. Integrins are integral cell-surface receptors that participate in cell adhesion as well as cell-surface mediated signaling. The alphav beta5 integrin is involved in adhesion to vitronectin. [provided by RefSeq, Aug 2017]

ITGB5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity ITB5_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0037605464).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB5	NM_002213.5 link	c.1430A>G	p.Asn477Ser	missense_variant	Exon 10 of 15	ENST00000296181.9	NP_002204.2	P18084L7RT22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB5	ENST00000296181.9 link	c.1430A>G	p.Asn477Ser	missense_variant	Exon 10 of 15	1	NM_002213.5	ENSP00000296181.4		P18084

Frequencies

GnomAD3 genomes

AF:

0.0481

AC:

7325

AN:

152164

Hom.:

252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0848

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0434

Gnomad ASJ

AF:

0.0335

Gnomad EAS

AF:

0.0328

Gnomad SAS

AF:

0.0892

Gnomad FIN

AF:

0.0234

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0436

AC:

10911

AN:

250414

AF XY:

0.0452

show subpopulations

Gnomad AFR exome

AF:

0.0887

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.0324

Gnomad FIN exome

AF:

0.0230

Gnomad NFE exome

AF:

0.0295

Gnomad OTH exome

AF:

0.0350

GnomAD4 exome

AF:

0.0358

AC:

52289

AN:

1461668

Hom.:

1262

Cov.:

AF XY:

0.0371

AC XY:

26999

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.0885

AC:

2963

AN:

33478

American (AMR)

AF:

0.0499

AC:

2232

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

738

AN:

26120

East Asian (EAS)

AF:

0.0419

AC:

1664

AN:

39698

South Asian (SAS)

AF:

0.0918

AC:

7917

AN:

86234

European-Finnish (FIN)

AF:

0.0232

AC:

1236

AN:

53346

Middle Eastern (MID)

AF:

0.0306

AC:

176

AN:

5750

European-Non Finnish (NFE)

AF:

0.0297

AC:

33040

AN:

1111954

Other (OTH)

AF:

0.0385

AC:

2323

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

3282

6565

9847

13130

16412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1370

2740

4110

5480

6850

<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:

0.0482

AC:

7345

AN:

152282

Hom.:

254

Cov.:

AF XY:

0.0478

AC XY:

3562

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0848

AC:

3523

AN:

41566

American (AMR)

AF:

0.0439

AC:

671

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0335

AC:

116

AN:

3466

East Asian (EAS)

AF:

0.0329

AC:

170

AN:

5170

South Asian (SAS)

AF:

0.0897

AC:

433

AN:

4828

European-Finnish (FIN)

AF:

0.0234

AC:

248

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0307

AC:

2087

AN:

68014

Other (OTH)

AF:

0.0393

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

362

724

1087

1449

1811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0353

Hom.:

366

Bravo

AF:

0.0490

TwinsUK

AF:

0.0356

AC:

132

ALSPAC

AF:

0.0332

AC:

128

ESP6500AA

AF:

0.0878

AC:

387

ESP6500EA

AF:

0.0302

AC:

260

ExAC

AF:

0.0453

AC:

5504

Asia WGS

AF:

0.0510

AC:

179

AN:

3478

EpiCase

AF:

0.0287

EpiControl

AF:

0.0285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.7

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.16

T;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;.

PhyloP100

1.4

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.56

N;.

REVEL

Benign

0.28

Sift

Benign

0.77

T;.

Sift4G

Benign

0.65

T;.

Polyphen

0.0

B;.

Vest4

0.048

MPC

0.18

ClinPred

0.00073

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.024

gMVP

0.28

Mutation Taster

=98/2

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