chr12-55697019-C-A

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.1617G>T(p.Gln539His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,614,096 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 60 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 65 hom. )

Consequence

ITGA7
NM_002206.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.321

Publications

1 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, Orphanet, Labcorp Genetics (formerly Invitae)
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=0.0031561255).

BP6

Variant 12-55697019-C-A is Benign according to our data. Variant chr12-55697019-C-A is described in ClinVar as Benign. ClinVar VariationId is 129292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002206.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA7	NM_002206.3	MANE Select	c.1617G>T	p.Gln539His	missense	Exon 12 of 25	NP_002197.2	Q13683-7
ITGA7	NM_001410977.1		c.1749G>T	p.Gln583His	missense	Exon 13 of 26	NP_001397906.1	Q13683-1
ITGA7	NM_001144996.2		c.1629G>T	p.Gln543His	missense	Exon 12 of 25	NP_001138468.1	Q13683-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.1617G>T	p.Gln539His	missense	Exon 12 of 25	ENSP00000257879.7	Q13683-7
ITGA7	ENST00000553804.6	TSL:1	c.1629G>T	p.Gln543His	missense	Exon 12 of 25	ENSP00000452120.1	Q13683-3
ITGA7	ENST00000555728.5	TSL:5	c.1749G>T	p.Gln583His	missense	Exon 13 of 26	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2447

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00412

AC:

1034

AN:

251208

AF XY:

0.00295

show subpopulations

Gnomad AFR exome

AF:

0.0587

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00158

AC:

2316

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

971

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.0598

AC:

2002

AN:

33478

American (AMR)

AF:

0.00190

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000525

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1111996

Other (OTH)

AF:

0.00320

AC:

193

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

144

287

431

574

718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.0161

AC:

2451

AN:

152318

Hom.:

Cov.:

AF XY:

0.0157

AC XY:

1169

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0566

AC:

2352

AN:

41560

American (AMR)

AF:

0.00503

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68026

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

120

240

360

480

600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00541

Hom.:

Bravo

AF:

0.0185

ESP6500AA

AF:

0.0561

AC:

247

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00528

AC:

641

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Congenital muscular dystrophy due to integrin alpha-7 deficiency (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

0.12

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

0.32

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.2

REVEL

Benign

0.083

Sift

Benign

0.17

Sift4G

Benign

0.12

Polyphen

0.35

Vest4

0.29

MutPred

0.50

Gain of methylation at R586 (P = 0.0442)

MVP

0.51

MPC

0.19

ClinPred

0.018

GERP RS

3.5

Varity_R

0.16

gMVP

0.62

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over