rs61733050

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002206.3(ITGA7):c.1609C>T(p.Arg537Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,613,996 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R537Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0057 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 14 hom. )

Consequence

ITGA7
NM_002206.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.62

Publications

3 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=0.009601176).

BP6

Variant 12-55697027-G-A is Benign according to our data. Variant chr12-55697027-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0057 (868/152276) while in subpopulation AFR AF = 0.0201 (833/41546). AF 95% confidence interval is 0.0189. There are 8 homozygotes in GnomAd4. There are 416 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA7	NM_002206.3 link	c.1609C>T	p.Arg537Trp	missense_variant	Exon 12 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.1609C>T	p.Arg537Trp	missense_variant	Exon 12 of 25	1	NM_002206.3	ENSP00000257879.7		Q13683-7

Frequencies

GnomAD3 genomes

AF:

0.00570

AC:

868

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00153

AC:

383

AN:

251066

AF XY:

0.00108

show subpopulations

Gnomad AFR exome

AF:

0.0206

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000601

AC:

879

AN:

1461720

Hom.:

Cov.:

AF XY:

0.000527

AC XY:

383

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.0207

AC:

694

AN:

33476

American (AMR)

AF:

0.00105

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000702

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000630

AC:

AN:

1111968

Other (OTH)

AF:

0.000944

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00570

AC:

868

AN:

152276

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

416

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0201

AC:

833

AN:

41546

American (AMR)

AF:

0.00131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68032

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

133

177

221

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:

0.00209

Hom.:

Bravo

AF:

0.00654

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00180

AC:

218

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 13, 2017

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. -

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:2

Oct 25, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Apr 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

.;.;T;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

D;D;D;D;D

MetaRNN

Benign

0.0096

T;T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.2

.;.;.;.;M

PhyloP100

1.6

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.8

D;D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.017

D;D;D;D;D

Sift4G

Uncertain

0.020

D;D;D;D;D

Polyphen

0.98

D;.;.;D;D

Vest4

0.43

MVP

0.57

MPC

0.64

ClinPred

0.057

GERP RS

3.5

Varity_R

0.23

gMVP

0.54

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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