rs7971022

Variant summary

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

The NM_002206.3(ITGA7):ā€‹c.1965T>Cā€‹(p.Cys655Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 1,612,240 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.014 ( 29 hom., cov: 30)
Exomes š‘“: 0.021 ( 402 hom. )

Consequence

ITGA7
NM_002206.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.04
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]

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=-0.78).
BP6
Variant 12-55695560-A-G is Benign according to our data. Variant chr12-55695560-A-G is described in ClinVar as [Benign]. Clinvar id is 94036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695560-A-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.04 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0144 (2168/150850) while in subpopulation NFE AF= 0.0235 (1592/67778). AF 95% confidence interval is 0.0225. There are 29 homozygotes in gnomad4. There are 1012 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGA7NM_002206.3 linkuse as main transcriptc.1965T>C p.Cys655Cys synonymous_variant 14/25 ENST00000257879.11 NP_002197.2 Q13683-7Q4LE35

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGA7ENST00000257879.11 linkuse as main transcriptc.1965T>C p.Cys655Cys synonymous_variant 14/251 NM_002206.3 ENSP00000257879.7 Q13683-7

Frequencies

GnomAD3 genomes
AF:
0.0144
AC:
2166
AN:
150736
Hom.:
29
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00398
Gnomad AMI
AF:
0.00881
Gnomad AMR
AF:
0.00706
Gnomad ASJ
AF:
0.0153
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0203
Gnomad FIN
AF:
0.0119
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.0235
Gnomad OTH
AF:
0.0102
GnomAD3 exomes
AF:
0.0162
AC:
4066
AN:
251454
Hom.:
45
AF XY:
0.0171
AC XY:
2330
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00308
Gnomad AMR exome
AF:
0.00471
Gnomad ASJ exome
AF:
0.0180
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0210
Gnomad FIN exome
AF:
0.0124
Gnomad NFE exome
AF:
0.0234
Gnomad OTH exome
AF:
0.0150
GnomAD4 exome
AF:
0.0214
AC:
31306
AN:
1461390
Hom.:
402
Cov.:
33
AF XY:
0.0215
AC XY:
15596
AN XY:
727030
show subpopulations
Gnomad4 AFR exome
AF:
0.00341
Gnomad4 AMR exome
AF:
0.00543
Gnomad4 ASJ exome
AF:
0.0165
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0203
Gnomad4 FIN exome
AF:
0.0140
Gnomad4 NFE exome
AF:
0.0242
Gnomad4 OTH exome
AF:
0.0174
GnomAD4 genome
AF:
0.0144
AC:
2168
AN:
150850
Hom.:
29
Cov.:
30
AF XY:
0.0137
AC XY:
1012
AN XY:
73666
show subpopulations
Gnomad4 AFR
AF:
0.00396
Gnomad4 AMR
AF:
0.00705
Gnomad4 ASJ
AF:
0.0153
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0205
Gnomad4 FIN
AF:
0.0119
Gnomad4 NFE
AF:
0.0235
Gnomad4 OTH
AF:
0.0106
Alfa
AF:
0.0205
Hom.:
28
Bravo
AF:
0.0134
Asia WGS
AF:
0.00751
AC:
26
AN:
3478
EpiCase
AF:
0.0240
EpiControl
AF:
0.0212

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, criteria provided, single submitterclinical testingGeneDxMar 29, 2016This 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. -
Likely benign, no assertion criteria providedclinical testingGenetic 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 submitterclinical testingAthena DiagnosticsMar 31, 2020- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 10, 2013- -
Congenital muscular dystrophy due to integrin alpha-7 deficiency Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
4.6
DANN
Benign
0.57

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.

Other links and lift over

dbSNP: rs7971022; hg19: chr12-56089344; API