rs144699549

Positions:

chr12-55698924-G-A

Variant summary

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

The ENST00000257879.11(ITGA7):c.791-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000763 in 1,603,618 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00073 ( 9 hom. )

Consequence

ITGA7
ENST00000257879.11 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002657

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.887

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 (BayesDel_noAF=-0.86).

BP6

Variant 12-55698924-G-A is Benign according to our data. Variant chr12-55698924-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211212.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 = 0.00104 (158/152196) while in subpopulation EAS AF= 0.0087 (45/5170). AF 95% confidence interval is 0.00669. There are 3 homozygotes in gnomad4. There are 69 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.791-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.791-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002206.3	ENSP00000257879	A1	Q13683-7

Frequencies

GnomAD3 genomes

AF:

0.000980

AC:

149

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00888

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00301

AC:

676

AN:

224624

Hom.:

AF XY:

0.00249

AC XY:

305

AN XY:

122692

show subpopulations

Gnomad AFR exome

AF:

0.000594

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.000315

Gnomad EAS exome

AF:

0.00932

Gnomad SAS exome

AF:

0.000209

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000913

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.000734

AC:

1066

AN:

1451422

Hom.:

Cov.:

AF XY:

0.000670

AC XY:

483

AN XY:

721382

show subpopulations

Gnomad4 AFR exome

AF:

0.000721

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.00733

Gnomad4 SAS exome

AF:

0.000271

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000587

Gnomad4 OTH exome

AF:

0.00198

GnomAD4 genome

AF:

0.00104

AC:

158

AN:

152196

Hom.:

Cov.:

AF XY:

0.000927

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000819

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00870

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000627

Hom.:

Bravo

AF:

0.00171

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 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	Eurofins Ntd Llc (ga)	Oct 26, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 14, 2014	- -

not provided

Benign:2

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, 2023	ITGA7: BP4, BS1, BS2 -

ITGA7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 27, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Congenital muscular dystrophy due to integrin alpha-7 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.4

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.010

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