12-55701110-G-C

Variant summary

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

The NM_002206.3(ITGA7):ā€‹c.459C>Gā€‹(p.Ile153Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,614,234 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0062 ( 8 hom., cov: 33)
Exomes š‘“: 0.00059 ( 10 hom. )

Consequence

ITGA7
NM_002206.3 missense

Scores

18

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.231
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0035514534).
BP6
Variant 12-55701110-G-C is Benign according to our data. Variant chr12-55701110-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 258587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00616 (939/152346) while in subpopulation AFR AF= 0.0211 (879/41578). AF 95% confidence interval is 0.02. There are 8 homozygotes in gnomad4. There are 454 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITGA7NM_002206.3 linkuse as main transcriptc.459C>G p.Ile153Met missense_variant 4/25 ENST00000257879.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITGA7ENST00000257879.11 linkuse as main transcriptc.459C>G p.Ile153Met missense_variant 4/251 NM_002206.3 A1Q13683-7

Frequencies

GnomAD3 genomes
AF:
0.00615
AC:
936
AN:
152228
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0211
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00134
AC:
338
AN:
251382
Hom.:
1
AF XY:
0.00102
AC XY:
138
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.0182
Gnomad AMR exome
AF:
0.000896
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000592
AC:
865
AN:
1461888
Hom.:
10
Cov.:
32
AF XY:
0.000517
AC XY:
376
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0202
Gnomad4 AMR exome
AF:
0.00116
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00161
GnomAD4 genome
AF:
0.00616
AC:
939
AN:
152346
Hom.:
8
Cov.:
33
AF XY:
0.00609
AC XY:
454
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0211
Gnomad4 AMR
AF:
0.00301
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.000989
Hom.:
1
Bravo
AF:
0.00727
ESP6500AA
AF:
0.0193
AC:
85
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00186
AC:
226
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxSep 24, 2018- -
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsMay 03, 2017- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Congenital muscular dystrophy due to integrin alpha-7 deficiency Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.67
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
18
DANN
Benign
0.83
DEOGEN2
Benign
0.0094
.;.;T;.;T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.48
T;T;T;T;T
MetaRNN
Benign
0.0036
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;L;.;.;L
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.010
N;N;N;N;N
REVEL
Benign
0.045
Sift
Benign
0.12
T;T;T;T;T
Sift4G
Benign
0.31
T;T;T;T;T
Polyphen
0.0030
B;.;.;B;B
Vest4
0.23
MVP
0.25
MPC
0.17
ClinPred
0.0030
T
GERP RS
0.46
Varity_R
0.052
gMVP
0.41

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: rs149000088; hg19: chr12-56094894; COSMIC: COSV99059708; COSMIC: COSV99059708; API