chr10-32911628-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2

The NM_002211.4(ITGB1):ā€‹c.1751A>Gā€‹(p.Asn584Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

ITGB1
NM_002211.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26
Variant links:
Genes affected
ITGB1 (HGNC:6153): (integrin subunit beta 1) Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM1
In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity ITB1_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.40226102).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITGB1NM_002211.4 linkuse as main transcriptc.1751A>G p.Asn584Ser missense_variant 13/16 ENST00000302278.8
ITGB1NM_033668.2 linkuse as main transcriptc.1751A>G p.Asn584Ser missense_variant 12/16
ITGB1NM_133376.3 linkuse as main transcriptc.1751A>G p.Asn584Ser missense_variant 13/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITGB1ENST00000302278.8 linkuse as main transcriptc.1751A>G p.Asn584Ser missense_variant 13/161 NM_002211.4 P4P05556-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461884
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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:
0.0000378

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 GeneticsMar 01, 2023The c.1751A>G (p.N584S) alteration is located in exon 12 (coding exon 12) of the ITGB1 gene. This alteration results from a A to G substitution at nucleotide position 1751, causing the asparagine (N) at amino acid position 584 to be replaced by a serine (S). 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
0.082
BayesDel_addAF
Uncertain
0.068
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
.;T;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D;D;.
M_CAP
Benign
0.072
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Uncertain
0.72
D
MutationAssessor
Benign
1.3
L;L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Uncertain
0.54
Sift
Benign
0.10
T;T;T
Sift4G
Benign
0.15
T;T;T
Polyphen
0.85
P;P;P
Vest4
0.35
MutPred
0.40
Loss of catalytic residue at N584 (P = 0.0221);Loss of catalytic residue at N584 (P = 0.0221);Loss of catalytic residue at N584 (P = 0.0221);
MVP
0.84
MPC
0.65
ClinPred
0.72
D
GERP RS
5.9
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.8
Varity_R
0.098
gMVP
0.66

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: rs1016123180; hg19: chr10-33200556; API