Genetic Variant NM_002206.3:c.810G>A (chr12-55698898-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002206.3(ITGA7):c.810G>A(p.Gly270Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 1,612,572 control chromosomes in the GnomAD database, including 4,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G270G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.056 ( 338 hom., cov: 31)

Exomes 𝑓: 0.070 ( 3871 hom. )

Consequence

ITGA7
NM_002206.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0670

Publications

7 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 12-55698898-C-T is Benign according to our data. Variant chr12-55698898-C-T is described in ClinVar as Benign. ClinVar VariationId is 94046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.067 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0794 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
ITGA7	NM_002206.3	MANE Select	c.810G>A	p.Gly270Gly	synonymous	Exon 6 of 25	NP_002197.2
ITGA7	NM_001410977.1		c.942G>A	p.Gly314Gly	synonymous	Exon 7 of 26	NP_001397906.1
ITGA7	NM_001144996.2		c.822G>A	p.Gly274Gly	synonymous	Exon 6 of 25	NP_001138468.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.810G>A	p.Gly270Gly	synonymous	Exon 6 of 25	ENSP00000257879.7
ITGA7	ENST00000553804.6	TSL:1	c.822G>A	p.Gly274Gly	synonymous	Exon 6 of 25	ENSP00000452120.1
ITGA7	ENST00000555728.5	TSL:5	c.942G>A	p.Gly314Gly	synonymous	Exon 7 of 26	ENSP00000452387.1

Frequencies

GnomAD3 genomes

AF:

0.0556

AC:

8456

AN:

152106

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0705

Gnomad ASJ

AF:

0.0968

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0347

Gnomad FIN

AF:

0.0543

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0812

Gnomad OTH

AF:

0.0817

GnomAD2 exomes

AF:

0.0598

AC:

14631

AN:

244762

AF XY:

0.0613

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.0464

Gnomad ASJ exome

AF:

0.0975

Gnomad EAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.0579

Gnomad NFE exome

AF:

0.0818

Gnomad OTH exome

AF:

0.0791

GnomAD4 exome

AF:

0.0697

AC:

101859

AN:

1460348

Hom.:

3871

Cov.:

AF XY:

0.0697

AC XY:

50638

AN XY:

726392

show subpopulations

African (AFR)

AF:

0.0112

AC:

375

AN:

33466

American (AMR)

AF:

0.0488

AC:

2171

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.0959

AC:

2502

AN:

26092

East Asian (EAS)

AF:

0.000202

AC:

AN:

39676

South Asian (SAS)

AF:

0.0420

AC:

3611

AN:

86066

European-Finnish (FIN)

AF:

0.0603

AC:

3201

AN:

53112

Middle Eastern (MID)

AF:

0.111

AC:

639

AN:

5768

European-Non Finnish (NFE)

AF:

0.0769

AC:

85421

AN:

1111332

Other (OTH)

AF:

0.0652

AC:

3931

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

5392

10784

16176

21568

26960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3002

6004

9006

12008

15010

<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:

0.0555

AC:

8455

AN:

152224

Hom.:

338

Cov.:

AF XY:

0.0538

AC XY:

4003

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0130

AC:

539

AN:

41546

American (AMR)

AF:

0.0704

AC:

1076

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0968

AC:

336

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0355

AC:

171

AN:

4814

European-Finnish (FIN)

AF:

0.0543

AC:

577

AN:

10618

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0811

AC:

5516

AN:

67976

Other (OTH)

AF:

0.0803

AC:

170

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

394

789

1183

1578

1972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0656

Hom.:

456

Bravo

AF:

0.0553

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

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

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

-0.067

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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