chr10-15607699-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003638.3(ITGA8):c.1742A>C(p.Gln581Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 1,613,564 control chromosomes in the GnomAD database, including 5,873 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 393 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5480 hom. )

Consequence

ITGA8
NM_003638.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0950

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

renal hypodysplasia/aplasia 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
bilateral renal agenesis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ITGA8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030740798).

BP6

Variant 10-15607699-T-G is Benign according to our data. Variant chr10-15607699-T-G is described in ClinVar as Benign. ClinVar VariationId is 1183844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA8	NM_003638.3 link	c.1742A>C	p.Gln581Pro	missense_variant	Exon 17 of 30	ENST00000378076.4	NP_003629.2	P53708B4DN28
ITGA8	NM_001291494.2 link	c.1697A>C	p.Gln566Pro	missense_variant	Exon 16 of 29		NP_001278423.1	B4DN28
ITGA8	XM_011519752.3 link	c.1742A>C	p.Gln581Pro	missense_variant	Exon 17 of 24		XP_011518054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA8	ENST00000378076.4 link	c.1742A>C	p.Gln581Pro	missense_variant	Exon 17 of 30	1	NM_003638.3	ENSP00000367316.3		P53708

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9583

AN:

152166

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0682

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0991

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0903

Gnomad OTH

AF:

0.0702

GnomAD2 exomes

AF:

0.0686

AC:

17207

AN:

250954

AF XY:

0.0697

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0933

Gnomad OTH exome

AF:

0.0840

GnomAD4 exome

AF:

0.0818

AC:

119539

AN:

1461280

Hom.:

5480

Cov.:

AF XY:

0.0807

AC XY:

58683

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.0134

AC:

448

AN:

33470

American (AMR)

AF:

0.0488

AC:

2184

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2826

AN:

26114

East Asian (EAS)

AF:

0.000126

AC:

AN:

39690

South Asian (SAS)

AF:

0.0316

AC:

2724

AN:

86234

European-Finnish (FIN)

AF:

0.102

AC:

5422

AN:

53414

Middle Eastern (MID)

AF:

0.0589

AC:

340

AN:

5768

European-Non Finnish (NFE)

AF:

0.0908

AC:

100935

AN:

1111492

Other (OTH)

AF:

0.0771

AC:

4655

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

5356

10712

16067

21423

26779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3610

7220

10830

14440

18050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0629

AC:

9586

AN:

152284

Hom.:

393

Cov.:

AF XY:

0.0628

AC XY:

4679

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0148

AC:

615

AN:

41572

American (AMR)

AF:

0.0682

AC:

1042

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

363

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5178

South Asian (SAS)

AF:

0.0292

AC:

141

AN:

4822

European-Finnish (FIN)

AF:

0.0991

AC:

1051

AN:

10602

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0903

AC:

6143

AN:

68030

Other (OTH)

AF:

0.0695

AC:

147

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

449

899

1348

1798

2247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0791

Hom.:

1274

Bravo

AF:

0.0583

TwinsUK

AF:

0.0941

AC:

349

ALSPAC

AF:

0.0880

AC:

339

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.0903

AC:

777

ExAC

AF:

0.0686

AC:

8330

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0930

EpiControl

AF:

0.0961

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 09, 2021

GeneDx

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

Uncertain

0.52

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.7

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.33

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

0.095

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.073

Sift

Benign

0.031

Sift4G

Benign

0.089

Polyphen

0.55

Vest4

0.22

MPC

0.19

ClinPred

0.052

GERP RS

-2.0

Varity_R

0.44

gMVP

0.83

Mutation Taster

=85/15

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over