rs11171663

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001144997.2(ITGA7):c.38C>T(p.Thr13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,551,446 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 15 hom., cov: 33)

Exomes 𝑓: 0.012 ( 138 hom. )

Consequence

ITGA7
NM_001144997.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.21

Publications

12 publications found

Variant links:

Genes affected

ITGA7 (HGNC:6143): (integrin subunit alpha 7) The protein encoded by this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. They mediate a wide spectrum of cell-cell and cell-matrix interactions, and thus play a role in cell migration, morphologic development, differentiation, and metastasis. This protein functions as a receptor for the basement membrane protein laminin-1. It is mainly expressed in skeletal and cardiac muscles and may be involved in differentiation and migration processes during myogenesis. Defects in this gene are associated with congenital myopathy. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2009]

ITGA7 Gene-Disease associations (from GenCC):

congenital muscular dystrophy due to integrin alpha-7 deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
congenital fiber-type disproportion myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ITGA7 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=0.0033804476).

BP6

Variant 12-55712110-G-A is Benign according to our data. Variant chr12-55712110-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 586038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00922 (1404/152330) while in subpopulation NFE AF = 0.0155 (1054/68028). AF 95% confidence interval is 0.0147. There are 15 homozygotes in GnomAd4. There are 645 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ITGA7	NM_001144997.2 link	c.38C>T	p.Thr13Ile	missense_variant	Exon 2 of 25	NP_001138469.1	Q13683-13Q4LE35
ITGA7	NM_001367993.1 link	c.-181C>T		5_prime_UTR_variant	Exon 2 of 26	NP_001354922.1
ITGA7	NM_001414035.1 link	c.-181C>T		5_prime_UTR_variant	Exon 1 of 25	NP_001400964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
ITGA7	ENST00000452168.6 link	c.38C>T	p.Thr13Ile	missense_variant	Exon 2 of 25	2	ENSP00000393844.2	Q13683-13
ITGA7	ENST00000553276.1 link	n.95C>T		non_coding_transcript_exon_variant	Exon 1 of 5	5
ITGA7	ENST00000553737.5 link	n.144C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00924

AC:

1406

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00941

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00861

AC:

1325

AN:

153832

AF XY:

0.00882

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.00506

Gnomad ASJ exome

AF:

0.00553

Gnomad EAS exome

AF:

0.000183

Gnomad FIN exome

AF:

0.00910

Gnomad NFE exome

AF:

0.0146

Gnomad OTH exome

AF:

0.00577

GnomAD4 exome

AF:

0.0123

AC:

17207

AN:

1399116

Hom.:

138

Cov.:

AF XY:

0.0122

AC XY:

8445

AN XY:

690076

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

31588

American (AMR)

AF:

0.00560

AC:

200

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00552

AC:

139

AN:

25178

East Asian (EAS)

AF:

0.0000839

AC:

AN:

35738

South Asian (SAS)

AF:

0.00464

AC:

368

AN:

79226

European-Finnish (FIN)

AF:

0.00992

AC:

489

AN:

49280

Middle Eastern (MID)

AF:

0.00861

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0142

AC:

15282

AN:

1078734

Other (OTH)

AF:

0.0108

AC:

629

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

852

1704

2557

3409

4261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.00922

AC:

1404

AN:

152330

Hom.:

Cov.:

AF XY:

0.00866

AC XY:

645

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00217

AC:

AN:

41568

American (AMR)

AF:

0.00667

AC:

102

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.00311

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00941

AC:

100

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0155

AC:

1054

AN:

68028

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0124

Hom.:

Bravo

AF:

0.00858

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00289

AC:

ESP6500EA

AF:

0.00943

AC:

ExAC

AF:

0.00654

AC:

155

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ITGA7: BP4, BS1, BS2 -

Jul 28, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 10, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.96

PhyloP100

1.2

PROVEAN

Benign

-1.1

REVEL

Benign

0.064

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0080

Vest4

0.10

MVP

0.30

ClinPred

0.017

GERP RS

1.4

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=92/8

polymorphism

(source)

Splicing

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