rs7895372

Variant names:

Variant summary

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

The NM_003638.3(ITGA8):c.646G>C(p.Val216Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,613,238 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.028 ( 185 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 184 hom. )

Consequence

ITGA8
NM_003638.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.01

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=0.0024095178).

BP6

Variant 10-15677622-C-G is Benign according to our data. Variant chr10-15677622-C-G is described in ClinVar as [Benign]. Clinvar id is 776499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA8	NM_003638.3 link	c.646G>C	p.Val216Leu	missense_variant	Exon 6 of 30	ENST00000378076.4	NP_003629.2	P53708B4DN28
ITGA8	NM_001291494.2 link	c.646G>C	p.Val216Leu	missense_variant	Exon 6 of 29		NP_001278423.1	B4DN28
ITGA8	XM_011519752.3 link	c.646G>C	p.Val216Leu	missense_variant	Exon 6 of 24		XP_011518054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA8	ENST00000378076.4 link	c.646G>C	p.Val216Leu	missense_variant	Exon 6 of 30	1	NM_003638.3	ENSP00000367316.3		P53708

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4213

AN:

152060

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00990

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00751

AC:

1884

AN:

250848

Hom.:

AF XY:

0.00528

AC XY:

716

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000300

Gnomad OTH exome

AF:

0.00410

GnomAD4 exome

AF:

0.00287

AC:

4197

AN:

1461060

Hom.:

184

Cov.:

AF XY:

0.00248

AC XY:

1802

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.0988

Gnomad4 AMR exome

AF:

0.00580

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.00600

GnomAD4 genome

AF:

0.0278

AC:

4233

AN:

152178

Hom.:

185

Cov.:

AF XY:

0.0264

AC XY:

1963

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0969

Gnomad4 AMR

AF:

0.00989

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00508

Hom.:

Bravo

AF:

0.0331

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.103

AC:

453

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00930

AC:

1129

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.054

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.58

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.96

REVEL

Benign

0.086

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.025

Vest4

0.34

MutPred

0.35

Gain of sheet (P = 0.1208);

MVP

0.49

MPC

0.073

ClinPred

0.0079

GERP RS

4.6

Varity_R

0.039

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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