rs113651939

Positions:

chr12-55693152-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002206.3(ITGA7):c.2701A>G(p.Ile901Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,613,798 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00097 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00075 ( 9 hom. )

Consequence

ITGA7
NM_002206.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.47

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:

ITGA7 (HGNC:):

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=0.009287894).

BP6

Variant 12-55693152-T-C is Benign according to our data. Variant chr12-55693152-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 211211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000967 (147/152002) while in subpopulation EAS AF= 0.00838 (43/5130). AF 95% confidence interval is 0.0064. There are 3 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA7	NM_002206.3 linkuse as main transcript	c.2701A>G	p.Ile901Val	missense_variant	20/25	ENST00000257879.11	NP_002197.2	Q13683-7Q4LE35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11 linkuse as main transcript	c.2701A>G	p.Ile901Val	missense_variant	20/25	1	NM_002206.3	ENSP00000257879.7		Q13683-7

Frequencies

GnomAD3 genomes

AF:

0.000909

AC:

138

AN:

151884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00361

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00856

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00295

AC:

741

AN:

251328

Hom.:

AF XY:

0.00242

AC XY:

329

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.0151

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00908

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.000752

AC:

1100

AN:

1461796

Hom.:

Cov.:

AF XY:

0.000682

AC XY:

496

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00728

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.000967

AC:

147

AN:

152002

Hom.:

Cov.:

AF XY:

0.000902

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.000748

Gnomad4 AMR

AF:

0.00367

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00838

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000551

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00256

AC:

311

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 26, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 14, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 18, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	ITGA7: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital muscular dystrophy due to integrin alpha-7 deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0022

.;.;T;.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.87

D;D;D;D;D

MetaRNN

Benign

0.0093

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;.;.;.;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.31

N;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.22

T;T;T;T;T

Sift4G

Benign

0.40

T;T;T;T;T

Polyphen

0.024

B;.;.;B;B

Vest4

0.20

MVP

0.40

MPC

0.14

ClinPred

0.0047

GERP RS

2.6

Varity_R

0.025

gMVP

0.18

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

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