rs11171663

Positions:

chr12-55712110-G-A

Variant summary

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

The NM_001144997.2(ITGA7):c.38C>T(p.Thr13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,551,446 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 15 hom., cov: 33)

Exomes 𝑓: 0.012 ( 138 hom. )

Consequence

ITGA7
NM_001144997.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.21

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=0.0033804476).

BP6

Variant 12-55712110-G-A is Benign according to our data. Variant chr12-55712110-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 586038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55712110-G-A is described in Lovd as [Benign]. Variant chr12-55712110-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00922 (1404/152330) while in subpopulation NFE AF= 0.0155 (1054/68028). AF 95% confidence interval is 0.0147. There are 15 homozygotes in gnomad4. There are 645 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
ITGA7	NM_001144997.2 linkuse as main transcript	c.38C>T	p.Thr13Ile	missense_variant	2/25	NP_001138469.1	Q13683-13Q4LE35
ITGA7	NM_001367993.1 linkuse as main transcript	c.-181C>T		5_prime_UTR_variant	2/26	NP_001354922.1
ITGA7	NM_001414035.1 linkuse as main transcript	c.-181C>T		5_prime_UTR_variant	1/25	NP_001400964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
ITGA7	ENST00000452168.6 linkuse as main transcript	c.38C>T	p.Thr13Ile	missense_variant	2/25	2	ENSP00000393844.2	Q13683-13
ITGA7	ENST00000557257.2 linkuse as main transcript	c.-108C>T		5_prime_UTR_variant	1/23	4	ENSP00000450578.2	G3V2C6
ITGA7	ENST00000553276.1 linkuse as main transcript	n.95C>T		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.00924

AC:

1406

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00941

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00861

AC:

1325

AN:

153832

Hom.:

AF XY:

0.00882

AC XY:

720

AN XY:

81612

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.00506

Gnomad ASJ exome

AF:

0.00553

Gnomad EAS exome

AF:

0.000183

Gnomad SAS exome

AF:

0.00426

Gnomad FIN exome

AF:

0.00910

Gnomad NFE exome

AF:

0.0146

Gnomad OTH exome

AF:

0.00577

GnomAD4 exome

AF:

0.0123

AC:

17207

AN:

1399116

Hom.:

138

Cov.:

AF XY:

0.0122

AC XY:

8445

AN XY:

690076

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.00560

Gnomad4 ASJ exome

AF:

0.00552

Gnomad4 EAS exome

AF:

0.0000839

Gnomad4 SAS exome

AF:

0.00464

Gnomad4 FIN exome

AF:

0.00992

Gnomad4 NFE exome

AF:

0.0142

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00922

AC:

1404

AN:

152330

Hom.:

Cov.:

AF XY:

0.00866

AC XY:

645

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00941

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.00858

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00289

AC:

ESP6500EA

AF:

0.00943

AC:

ExAC

AF:

0.00654

AC:

155

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	ITGA7: BP4, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 23, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.96

PROVEAN

Benign

-1.1

REVEL

Benign

0.064

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0080

Vest4

0.10

MVP

0.30

ClinPred

0.017

GERP RS

1.4

Splicing

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