chr7-20394905-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002214.3(ITGB8):c.1066C>A(p.Pro356Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,611,764 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 (★).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
ITGB8
NM_002214.3 missense
NM_002214.3 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 4.15
Genes affected
ITGB8 (HGNC:6163): (integrin subunit beta 8) This gene is a member of the integrin beta chain family and encodes a single-pass type I membrane protein with a VWFA domain and four cysteine-rich repeats. This protein noncovalently binds to an alpha subunit to form a heterodimeric integrin complex. In general, integrin complexes mediate cell-cell and cell-extracellular matrix interactions and this complex plays a role in human airway epithelial proliferation. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16405103).
BS2
?
High AC in GnomAd at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGB8 | NM_002214.3 | c.1066C>A | p.Pro356Thr | missense_variant | 8/14 | ENST00000222573.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGB8 | ENST00000222573.5 | c.1066C>A | p.Pro356Thr | missense_variant | 8/14 | 1 | NM_002214.3 | P1 | |
ITGB8 | ENST00000478974.1 | n.1771C>A | non_coding_transcript_exon_variant | 8/9 | 1 | ||||
ITGB8 | ENST00000537992.5 | c.661C>A | p.Pro221Thr | missense_variant | 9/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152196Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
12
AN:
152196
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251292Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135828
GnomAD3 exomes
AF:
AC:
6
AN:
251292
Hom.:
AF XY:
AC XY:
1
AN XY:
135828
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000891 AC: 13AN: 1459450Hom.: 0 Cov.: 29 AF XY: 0.00000688 AC XY: 5AN XY: 726278
GnomAD4 exome
AF:
AC:
13
AN:
1459450
Hom.:
Cov.:
29
AF XY:
AC XY:
5
AN XY:
726278
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74484
GnomAD4 genome
?
AF:
AC:
15
AN:
152314
Hom.:
Cov.:
33
AF XY:
AC XY:
7
AN XY:
74484
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
2
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
4
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 submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | The c.1066C>A (p.P356T) alteration is located in exon 8 (coding exon 8) of the ITGB8 gene. This alteration results from a C to A substitution at nucleotide position 1066, causing the proline (P) at amino acid position 356 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.88
.;P
Vest4
MVP
MPC
0.44
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at