dbSNP rs375058260: ITGB5:p.Arg514Leu (chr3-124796540-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002213.5(ITGB5):c.1541G>T(p.Arg514Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R514Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITGB5
NM_002213.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.86

Publications

0 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:

LOC124909422 (HGNC:):

LOC124909422 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGB5	NM_002213.5	MANE Select	c.1541G>T	p.Arg514Leu	missense	Exon 10 of 15	NP_002204.2
ITGB5	NM_001354764.2		c.1217G>T	p.Arg406Leu	missense	Exon 10 of 15	NP_001341693.1
ITGB5	NM_001354765.1		c.1217G>T	p.Arg406Leu	missense	Exon 10 of 15	NP_001341694.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGB5	ENST00000296181.9	TSL:1 MANE Select	c.1541G>T	p.Arg514Leu	missense	Exon 10 of 15	ENSP00000296181.4	P18084
ITGB5	ENST00000905025.1		c.1763G>T	p.Arg588Leu	missense	Exon 12 of 17	ENSP00000575084.1
ITGB5	ENST00000965613.1		c.1655G>T	p.Arg552Leu	missense	Exon 12 of 17	ENSP00000635672.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

0.60

MutationAssessor

Benign

-0.015

PhyloP100

4.9

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.2

REVEL

Pathogenic

0.67

Sift

Benign

0.066

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.66

MutPred

0.49

Gain of catalytic residue at R514 (P = 0.0124)

MVP

0.97

MPC

0.82

ClinPred

0.98

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.83

Mutation Taster

=53/47

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over