12-55698884-C-T

Variant names:

Variant summary

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

The NM_002206.3(ITGA7):c.824G>A(p.Arg275His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 1,613,422 control chromosomes in the GnomAD database, including 2,301 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R275L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.033 ( 128 hom., cov: 31)

Exomes 𝑓: 0.050 ( 2173 hom. )

Consequence

ITGA7
NM_002206.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0750

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=0.0020250678).

BP6

Variant 12-55698884-C-T is Benign according to our data. Variant chr12-55698884-C-T is described in ClinVar as [Benign]. Clinvar id is 94047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA7	NM_002206.3 link	c.824G>A	p.Arg275His	missense_variant	Exon 6 of 25	ENST00000257879.11	NP_002197.2	Q13683-7Q4LE35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11 link	c.824G>A	p.Arg275His	missense_variant	Exon 6 of 25	1	NM_002206.3	ENSP00000257879.7		Q13683-7

Frequencies

GnomAD3 genomes

AF:

0.0334

AC:

5073

AN:

152090

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.0406

GnomAD2 exomes

AF:

0.0328

AC:

8125

AN:

247600

AF XY:

0.0332

show subpopulations

Gnomad AFR exome

AF:

0.00897

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0453

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.0528

Gnomad OTH exome

AF:

0.0315

GnomAD4 exome

AF:

0.0504

AC:

73659

AN:

1461214

Hom.:

2173

Cov.:

AF XY:

0.0494

AC XY:

35892

AN XY:

726876

show subpopulations

African (AFR)

AF:

0.00911

AC:

305

AN:

33470

American (AMR)

AF:

0.0144

AC:

645

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.0463

AC:

1210

AN:

26124

East Asian (EAS)

AF:

0.000151

AC:

AN:

39696

South Asian (SAS)

AF:

0.0212

AC:

1825

AN:

86178

European-Finnish (FIN)

AF:

0.0220

AC:

1172

AN:

53226

Middle Eastern (MID)

AF:

0.0227

AC:

131

AN:

5768

European-Non Finnish (NFE)

AF:

0.0589

AC:

65487

AN:

1111742

Other (OTH)

AF:

0.0477

AC:

2878

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

4140

8281

12421

16562

20702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0333

AC:

5075

AN:

152208

Hom.:

128

Cov.:

AF XY:

0.0303

AC XY:

2255

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0101

AC:

419

AN:

41514

American (AMR)

AF:

0.0232

AC:

354

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0172

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0165

AC:

175

AN:

10628

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0551

AC:

3749

AN:

67980

Other (OTH)

AF:

0.0402

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

241

481

722

962

1203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0422

Hom.:

332

Bravo

AF:

0.0333

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0594

AC:

229

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.0528

AC:

454

ExAC

AF:

0.0331

AC:

4019

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0522

EpiControl

AF:

0.0494

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 10, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mar 15, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital muscular dystrophy due to integrin alpha-7 deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

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

0.084

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0085

.;.;T;.;T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.65

T;T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

.;.;.;.;N;.

PhyloP100

-0.075

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.5

N;N;N;N;N;N

REVEL

Benign

0.025

Sift

Benign

0.20

T;T;T;T;T;T

Sift4G

Benign

0.36

T;T;T;T;T;.

Polyphen

0.012

B;.;.;B;B;.

Vest4

0.17

MPC

0.22

ClinPred

0.018

GERP RS

2.6

Varity_R

0.050

gMVP

0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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12-55698884-C-T

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