3-124773748-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002213.5(ITGB5):​c.1858G>T​(p.Ala620Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A620T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITGB5
NM_002213.5 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22822344).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGB5NM_002213.5 linkc.1858G>T p.Ala620Ser missense_variant Exon 11 of 15 ENST00000296181.9 NP_002204.2 P18084L7RT22

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGB5ENST00000296181.9 linkc.1858G>T p.Ala620Ser missense_variant Exon 11 of 15 1 NM_002213.5 ENSP00000296181.4 P18084
ITGB5ENST00000481591.5 linkc.925G>T p.Ala309Ser missense_variant Exon 5 of 7 5 ENSP00000420814.1 H7C5U2
ITGB5ENST00000461306.1 linkn.197G>T non_coding_transcript_exon_variant Exon 2 of 5 4
ITGB5ENST00000488466.5 linkc.*71G>T downstream_gene_variant 5 ENSP00000477446.1 V9GZ57

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460492
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726576
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.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.012
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.16
Eigen_PC
Benign
0.040
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
0.17
N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.32
Sift
Benign
0.30
T
Sift4G
Benign
0.46
T
Polyphen
0.16
B
Vest4
0.23
MutPred
0.50
Loss of catalytic residue at A620 (P = 0.0024);
MVP
0.95
MPC
0.26
ClinPred
0.66
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.095
gMVP
0.69

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: chr3-124492595; API