10-32920355-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_002211.4(ITGB1):​c.1159G>A​(p.Gly387Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,613,216 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

ITGB1
NM_002211.4 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.88
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07574007).
BP6
Variant 10-32920355-C-T is Benign according to our data. Variant chr10-32920355-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2357692.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGB1NM_002211.4 linkuse as main transcriptc.1159G>A p.Gly387Ser missense_variant 10/16 ENST00000302278.8 NP_002202.2
ITGB1NM_033668.2 linkuse as main transcriptc.1159G>A p.Gly387Ser missense_variant 9/16 NP_391988.1
ITGB1NM_133376.3 linkuse as main transcriptc.1159G>A p.Gly387Ser missense_variant 10/16 NP_596867.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGB1ENST00000302278.8 linkuse as main transcriptc.1159G>A p.Gly387Ser missense_variant 10/161 NM_002211.4 ENSP00000303351 P4P05556-1

Frequencies

GnomAD3 genomes
AF:
0.0000658
AC:
10
AN:
152064
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000797
AC:
20
AN:
250890
Hom.:
0
AF XY:
0.0000959
AC XY:
13
AN XY:
135596
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000177
AC:
258
AN:
1461152
Hom.:
0
Cov.:
31
AF XY:
0.000180
AC XY:
131
AN XY:
726908
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000225
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000658
AC:
10
AN:
152064
Hom.:
0
Cov.:
31
AF XY:
0.0000539
AC XY:
4
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000196
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 06, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
1.8
DANN
Benign
0.71
DEOGEN2
Uncertain
0.50
.;T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.27
T;T;.
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.076
T;T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
-1.7
N;N;N
MutationTaster
Benign
0.95
N;N;N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
1.7
N;N;N
REVEL
Benign
0.29
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.064
MVP
0.48
MPC
0.77
ClinPred
0.023
T
GERP RS
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.083

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs201962041; hg19: chr10-33209283; API