chr12-55698884-C-T

Position:

chr12-55698884-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr12-55698884-C-T is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
ITGA7	NM_002206.3 linkuse as main transcript	c.824G>A	p.Arg275His	missense_variant	6/25	ENST00000257879.11	NP_002197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11 linkuse as main transcript	c.824G>A	p.Arg275His	missense_variant	6/25	1	NM_002206.3	ENSP00000257879	A1	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

GnomAD3 exomes

AF:

0.0328

AC:

8125

AN:

247600

Hom.:

204

AF XY:

0.0332

AC XY:

4463

AN XY:

134400

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 SAS exome

AF:

0.0185

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

Gnomad4 AFR exome

AF:

0.00911

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0463

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0212

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.0589

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.0333

AC:

5075

AN:

152208

Hom.:

128

Cov.:

AF XY:

0.0303

AC XY:

2255

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0172

Gnomad4 FIN

AF:

0.0165

Gnomad4 NFE

AF:

0.0551

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0454

Hom.:

245

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 10, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -

Congenital muscular dystrophy due to integrin alpha-7 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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;.

MutationTaster

Benign

0.63

D;D;D;D;D;D;D;D

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over