3-124796776-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002213.5(ITGB5):ā€‹c.1305C>Gā€‹(p.Ser435Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,612,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00039 ( 0 hom., cov: 33)
Exomes š‘“: 0.000034 ( 0 hom. )

Consequence

ITGB5
NM_002213.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0680
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016452432).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGB5NM_002213.5 linkuse as main transcriptc.1305C>G p.Ser435Arg missense_variant 10/15 ENST00000296181.9 NP_002204.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGB5ENST00000296181.9 linkuse as main transcriptc.1305C>G p.Ser435Arg missense_variant 10/151 NM_002213.5 ENSP00000296181 P1

Frequencies

GnomAD3 genomes
AF:
0.000381
AC:
58
AN:
152252
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00140
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000101
AC:
25
AN:
248454
Hom.:
0
AF XY:
0.0000521
AC XY:
7
AN XY:
134420
show subpopulations
Gnomad AFR exome
AF:
0.00119
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000336
AC:
49
AN:
1460212
Hom.:
0
Cov.:
33
AF XY:
0.0000289
AC XY:
21
AN XY:
726138
show subpopulations
Gnomad4 AFR exome
AF:
0.000987
Gnomad4 AMR exome
AF:
0.000112
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:
0.00000180
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000387
AC:
59
AN:
152370
Hom.:
0
Cov.:
33
AF XY:
0.000309
AC XY:
23
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.00142
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000476
ESP6500AA
AF:
0.00250
AC:
11
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000124
AC:
15

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 06, 2021The c.1305C>G (p.S435R) alteration is located in exon 10 (coding exon 10) of the ITGB5 gene. This alteration results from a C to G substitution at nucleotide position 1305, causing the serine (S) at amino acid position 435 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
13
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.43
T;T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.016
T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
-0.24
N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.2
N;.
REVEL
Benign
0.18
Sift
Benign
0.30
T;.
Sift4G
Benign
0.49
T;.
Polyphen
0.25
B;.
Vest4
0.26
MutPred
0.46
Gain of solvent accessibility (P = 0.005);.;
MVP
0.98
MPC
0.29
ClinPred
0.022
T
GERP RS
3.3
Varity_R
0.028
gMVP
0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141196770; hg19: chr3-124515623; API