dbSNP rs17117883: ITGA7:p.Ser1006Ser (chr12-55688241-G-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002206.3(ITGA7):c.3018C>G(p.Ser1006Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 1,613,858 control chromosomes in the GnomAD database, including 2,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 217 hom., cov: 31)

Exomes 𝑓: 0.049 ( 1957 hom. )

Consequence

ITGA7
NM_002206.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.997

Publications

9 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 12-55688241-G-C is Benign according to our data. Variant chr12-55688241-G-C is described in ClinVar as Benign. ClinVar VariationId is 129294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.997 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 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.3018C>G	p.Ser1006Ser	synonymous	Exon 23 of 25	NP_002197.2	Q13683-7
ITGA7	NM_001410977.1		c.3150C>G	p.Ser1050Ser	synonymous	Exon 24 of 26	NP_001397906.1	Q13683-1
ITGA7	NM_001144996.2		c.3030C>G	p.Ser1010Ser	synonymous	Exon 23 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.3018C>G	p.Ser1006Ser	synonymous	Exon 23 of 25	ENSP00000257879.7	Q13683-7
ITGA7	ENST00000553804.6	TSL:1	c.3030C>G	p.Ser1010Ser	synonymous	Exon 23 of 25	ENSP00000452120.1	Q13683-3
ITGA7	ENST00000555728.5	TSL:5	c.3150C>G	p.Ser1050Ser	synonymous	Exon 24 of 26	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes

AF:

0.0496

AC:

7542

AN:

152096

Hom.:

215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0645

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0420

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0466

Gnomad FIN

AF:

0.0196

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.0575

GnomAD2 exomes

AF:

0.0410

AC:

10297

AN:

251448

AF XY:

0.0428

show subpopulations

Gnomad AFR exome

AF:

0.0641

Gnomad AMR exome

AF:

0.0227

Gnomad ASJ exome

AF:

0.0414

Gnomad EAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.0228

Gnomad NFE exome

AF:

0.0495

Gnomad OTH exome

AF:

0.0443

GnomAD4 exome

AF:

0.0489

AC:

71483

AN:

1461644

Hom.:

1957

Cov.:

AF XY:

0.0495

AC XY:

35981

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.0633

AC:

2118

AN:

33462

American (AMR)

AF:

0.0249

AC:

1113

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0382

AC:

999

AN:

26134

East Asian (EAS)

AF:

0.000831

AC:

AN:

39698

South Asian (SAS)

AF:

0.0536

AC:

4621

AN:

86250

European-Finnish (FIN)

AF:

0.0218

AC:

1167

AN:

53420

Middle Eastern (MID)

AF:

0.0756

AC:

436

AN:

5768

European-Non Finnish (NFE)

AF:

0.0522

AC:

58090

AN:

1111804

Other (OTH)

AF:

0.0481

AC:

2906

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

3808

7616

11424

15232

19040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2196

4392

6588

8784

10980

<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:

0.0496

AC:

7550

AN:

152214

Hom.:

217

Cov.:

AF XY:

0.0478

AC XY:

3561

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0644

AC:

2674

AN:

41496

American (AMR)

AF:

0.0420

AC:

643

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

127

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0473

AC:

228

AN:

4824

European-Finnish (FIN)

AF:

0.0196

AC:

208

AN:

10612

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0508

AC:

3454

AN:

68022

Other (OTH)

AF:

0.0569

AC:

120

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

359

718

1076

1435

1794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0518

Hom.:

Bravo

AF:

0.0499

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0541

EpiControl

AF:

0.0528

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

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

-0.61

CADD

Benign

4.7

(source)

DANN

Benign

0.86

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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