rs17854601

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002206.3(ITGA7):c.285G>T(p.Pro95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,614,030 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 28 hom., cov: 33)

Exomes 𝑓: 0.024 ( 495 hom. )

Consequence

ITGA7
NM_002206.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.03

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-55703100-C-A is Benign according to our data. Variant chr12-55703100-C-A is described in ClinVar as [Benign]. Clinvar id is 129293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55703100-C-A is described in Lovd as [Likely_benign]. Variant chr12-55703100-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.03 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0173 (2637/152292) while in subpopulation AMR AF= 0.0278 (425/15304). AF 95% confidence interval is 0.0256. There are 28 homozygotes in gnomad4. There are 1240 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA7	NM_002206.3 linkuse as main transcript	c.285G>T	p.Pro95=	synonymous_variant	2/25	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.285G>T	p.Pro95=	synonymous_variant	2/25	1	NM_002206.3	ENSP00000257879	A1	Q13683-7

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2641

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00446

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.0617

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0186

AC:

4673

AN:

250844

Hom.:

AF XY:

0.0190

AC XY:

2576

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.0231

Gnomad ASJ exome

AF:

0.0566

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00764

Gnomad FIN exome

AF:

0.00293

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.0236

AC:

34476

AN:

1461738

Hom.:

495

Cov.:

AF XY:

0.0234

AC XY:

16988

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00343

Gnomad4 AMR exome

AF:

0.0233

Gnomad4 ASJ exome

AF:

0.0582

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00854

Gnomad4 FIN exome

AF:

0.00400

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0173

AC:

2637

AN:

152292

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1240

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00443

Gnomad4 AMR

AF:

0.0278

Gnomad4 ASJ

AF:

0.0617

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00931

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0204

Hom.:

Bravo

AF:

0.0193

EpiCase

AF:

0.0299

EpiControl

AF:

0.0296

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	GeneDx	Feb 08, 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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 12, 2020	- -

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.9

DANN

Benign

0.79

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