Variant 7-20381839-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002214.3(ITGB8):c.914G>C(p.Gly305Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITGB8
NM_002214.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB8	NM_002214.3 linkuse as main transcript	c.914G>C	p.Gly305Ala	missense_variant	6/14	ENST00000222573.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB8	ENST00000222573.5 linkuse as main transcript	c.914G>C	p.Gly305Ala	missense_variant	6/14	1	NM_002214.3	P1	P26012-1
ITGB8	ENST00000477859.1 linkuse as main transcript	n.5331G>C		non_coding_transcript_exon_variant	2/2	1
ITGB8	ENST00000478974.1 linkuse as main transcript	n.1619G>C		non_coding_transcript_exon_variant	6/9	1
ITGB8	ENST00000537992.5 linkuse as main transcript	c.509G>C	p.Gly170Ala	missense_variant	7/15	2			P26012-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250990

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

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:

6.84e-7

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Cov.:

ExAC

AF:

0.00000824

AC:

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 29, 2023

The c.914G>C (p.G305A) alteration is located in exon 6 (coding exon 6) of the ITGB8 gene. This alteration results from a G to C substitution at nucleotide position 914, causing the glycine (G) at amino acid position 305 to be replaced by an alanine (A). 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

Pathogenic

0.65

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.31

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.97

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Pathogenic

0.92

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Pathogenic

0.77

Sift

Uncertain

0.012

D;D

Sift4G

Pathogenic

0.0

D;T

Polyphen

1.0

.;D

Vest4

0.86

MutPred

0.88

.;Loss of ubiquitination at K310 (P = 0.0777);

MVP

0.86

MPC

0.65

ClinPred

0.98

GERP RS

6.1

Varity_R

0.76

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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