Genetic Variant ITGB5:p.Ser473Ser (chr3-124796662-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_002213.5(ITGB5):c.1419C>T(p.Ser473Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,613,754 control chromosomes in the GnomAD database, including 24,068 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 0.16 ( 2254 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21814 hom. )

Consequence

ITGB5
NM_002213.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

Publications

17 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.178).

BP7

Synonymous conserved (PhyloP=2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB5	NM_002213.5 link	c.1419C>T	p.Ser473Ser	synonymous_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.1419C>T	p.Ser473Ser	synonymous_variant	Exon 10 of 15	1	NM_002213.5	ENSP00000296181.4		P18084

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24773

AN:

152046

Hom.:

2253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.0744

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.159

GnomAD2 exomes

AF:

0.182

AC:

45416

AN:

250072

AF XY:

0.176

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.0785

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.217

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.169

AC:

247507

AN:

1461590

Hom.:

21814

Cov.:

AF XY:

0.168

AC XY:

122113

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.123

AC:

4118

AN:

33480

American (AMR)

AF:

0.303

AC:

13548

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.0802

AC:

2095

AN:

26120

East Asian (EAS)

AF:

0.207

AC:

8207

AN:

39696

South Asian (SAS)

AF:

0.161

AC:

13922

AN:

86236

European-Finnish (FIN)

AF:

0.209

AC:

11137

AN:

53356

Middle Eastern (MID)

AF:

0.133

AC:

765

AN:

5742

European-Non Finnish (NFE)

AF:

0.166

AC:

184086

AN:

1111924

Other (OTH)

AF:

0.160

AC:

9629

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

13315

26630

39944

53259

66574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6668

13336

20004

26672

33340

<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:

0.163

AC:

24785

AN:

152164

Hom.:

2254

Cov.:

AF XY:

0.167

AC XY:

12385

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.127

AC:

5270

AN:

41542

American (AMR)

AF:

0.249

AC:

3805

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0744

AC:

258

AN:

3470

East Asian (EAS)

AF:

0.174

AC:

896

AN:

5156

South Asian (SAS)

AF:

0.158

AC:

763

AN:

4826

European-Finnish (FIN)

AF:

0.218

AC:

2306

AN:

10564

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

11000

AN:

68010

Other (OTH)

AF:

0.162

AC:

341

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1049

2098

3148

4197

5246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.148

Hom.:

2516

Bravo

AF:

0.163

Asia WGS

AF:

0.179

AC:

619

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.78

(source)

DANN

Benign

0.45

PhyloP100

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

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