rs2298033

Positions:

chr10-15607711-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003638.3(ITGA8):c.1730C>T(p.Ser577Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,613,792 control chromosomes in the GnomAD database, including 867 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.028 ( 115 hom., cov: 32)

Exomes 𝑓: 0.022 ( 752 hom. )

Consequence

ITGA8
NM_003638.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

ITGA8 (HGNC:6144): (integrin subunit alpha 8) Integrins are heterodimeric transmembrane receptor proteins that mediate numerous cellular processes including cell adhesion, cytoskeletal rearrangement, and activation of cell signaling pathways. Integrins are composed of alpha and beta subunits. This gene encodes the alpha 8 subunit of the heterodimeric integrin alpha8beta1 protein. The encoded protein is a single-pass type 1 membrane protein that contains multiple FG-GAP repeats. This repeat is predicted to fold into a beta propeller structure. This gene regulates the recruitment of mesenchymal cells into epithelial structures, mediates cell-cell interactions, and regulates neurite outgrowth of sensory and motor neurons. The integrin alpha8beta1 protein thus plays an important role in wound-healing and organogenesis. Mutations in this gene have been associated with renal hypodysplasia/aplasia-1 (RHDA1) and with several animal models of chronic kidney disease. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2014]

ITGA8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025519729).

BP6

Variant 10-15607711-G-A is Benign according to our data. Variant chr10-15607711-G-A is described in ClinVar as [Benign]. Clinvar id is 1238988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-15607711-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ITGA8	NM_003638.3 linkuse as main transcript	c.1730C>T	p.Ser577Phe	missense_variant	17/30	ENST00000378076.4	NP_003629.2
ITGA8	NM_001291494.2 linkuse as main transcript	c.1685C>T	p.Ser562Phe	missense_variant	16/29		NP_001278423.1
ITGA8	XM_011519752.3 linkuse as main transcript	c.1730C>T	p.Ser577Phe	missense_variant	17/24		XP_011518054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA8	ENST00000378076.4 linkuse as main transcript	c.1730C>T	p.Ser577Phe	missense_variant	17/30	1	NM_003638.3	ENSP00000367316	P1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4280

AN:

152120

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.0829

Gnomad SAS

AF:

0.00788

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0344

AC:

8642

AN:

251030

Hom.:

315

AF XY:

0.0310

AC XY:

4209

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.0592

Gnomad ASJ exome

AF:

0.00895

Gnomad EAS exome

AF:

0.0764

Gnomad SAS exome

AF:

0.00875

Gnomad FIN exome

AF:

0.0970

Gnomad NFE exome

AF:

0.0189

Gnomad OTH exome

AF:

0.0305

GnomAD4 exome

AF:

0.0215

AC:

31491

AN:

1461554

Hom.:

752

Cov.:

AF XY:

0.0207

AC XY:

15087

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.0537

Gnomad4 ASJ exome

AF:

0.00880

Gnomad4 EAS exome

AF:

0.0927

Gnomad4 SAS exome

AF:

0.00763

Gnomad4 FIN exome

AF:

0.0946

Gnomad4 NFE exome

AF:

0.0155

Gnomad4 OTH exome

AF:

0.0222

GnomAD4 genome

AF:

0.0281

AC:

4285

AN:

152238

Hom.:

115

Cov.:

AF XY:

0.0314

AC XY:

2337

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0263

Gnomad4 AMR

AF:

0.0257

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.0833

Gnomad4 SAS

AF:

0.00768

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0191

Hom.:

Bravo

AF:

0.0240

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.0141

AC:

121

ExAC

AF:

0.0322

AC:

3907

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

EpiCase

AF:

0.0144

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 23153507) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.21

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.14

Sift

Benign

0.053

Sift4G

Uncertain

0.055

Polyphen

0.43

Vest4

0.14

MPC

0.15

ClinPred

0.016

GERP RS

4.9

Varity_R

0.059

gMVP

0.43

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