chr3-124796540-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

1
13
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.86
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGB5NM_002213.5 linkc.1541G>T p.Arg514Leu 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
ITGB5ENST00000296181.9 linkc.1541G>T p.Arg514Leu missense_variant Exon 10 of 15 1 NM_002213.5 ENSP00000296181.4 P18084

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461768
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.73
D;T
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Uncertain
0.21
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Uncertain
0.60
D
MutationAssessor
Benign
-0.015
N;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-4.2
D;.
REVEL
Pathogenic
0.67
Sift
Benign
0.066
T;.
Sift4G
Benign
0.10
T;.
Polyphen
1.0
D;.
Vest4
0.66
MutPred
0.49
Gain of catalytic residue at R514 (P = 0.0124);.;
MVP
0.97
MPC
0.82
ClinPred
0.98
D
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.38
gMVP
0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-124515387; API