chr7-20398935-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002214.3(ITGB8):c.1222C>A(p.Pro408Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,611,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
ITGB8
NM_002214.3 missense
NM_002214.3 missense
Scores
3
9
5
Clinical Significance
Conservation
PhyloP100: 6.09
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGB8 | NM_002214.3 | c.1222C>A | p.Pro408Thr | missense_variant | 9/14 | ENST00000222573.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGB8 | ENST00000222573.5 | c.1222C>A | p.Pro408Thr | missense_variant | 9/14 | 1 | NM_002214.3 | P1 | |
ITGB8 | ENST00000478974.1 | n.1927C>A | non_coding_transcript_exon_variant | 9/9 | 1 | ||||
ITGB8 | ENST00000537992.5 | c.817C>A | p.Pro273Thr | missense_variant | 10/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250578Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135456
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GnomAD4 exome AF: 0.00000480 AC: 7AN: 1459836Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726282
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310
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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 | Oct 26, 2022 | The c.1222C>A (p.P408T) alteration is located in exon 9 (coding exon 9) of the ITGB8 gene. This alteration results from a C to A substitution at nucleotide position 1222, causing the proline (P) at amino acid position 408 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
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.95
.;P
Vest4
MutPred
0.54
.;Gain of phosphorylation at P408 (P = 0.0794);
MVP
MPC
0.63
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at