Variant 7-20331928-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002214.3(ITGB8):c.122A>G(p.Gln41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ITGB8
NM_002214.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Variant links:

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]

ITGB8 links:

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=0.09721738).

BS2

High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB8	NM_002214.3 linkuse as main transcript	c.122A>G	p.Gln41Arg	missense_variant	1/14	ENST00000222573.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB8	ENST00000222573.5 linkuse as main transcript	c.122A>G	p.Gln41Arg	missense_variant	1/14	1	NM_002214.3	P1	P26012-1
ITGB8	ENST00000478974.1 linkuse as main transcript	n.827A>G		non_coding_transcript_exon_variant	1/9	1
ITGB8	ENST00000537992.5 linkuse as main transcript	c.-325-49A>G		intron_variant		2			P26012-2
ITGB8	ENST00000460204.1 linkuse as main transcript			upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248516

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134606

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000169

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000453

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

Dec 28, 2022

The c.122A>G (p.Q41R) alteration is located in exon 1 (coding exon 1) of the ITGB8 gene. This alteration results from a A to G substitution at nucleotide position 122, causing the glutamine (Q) at amino acid position 41 to be replaced by an arginine (R). 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

0.063

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Benign

0.93

DEOGEN2

Benign

0.20

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.51

M_CAP

Benign

0.013

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.54

REVEL

Benign

0.24

Sift

Benign

0.31

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.11

MVP

0.61

MPC

0.15

ClinPred

0.11

GERP RS

1.7

Varity_R

0.20

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over