rs200267194

Variant names:

• chr12-55697047-G-A
• rs200267194
• NM_002206.3:c.1589C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-55697047-G-A
• chr12-55697047-G-C
• chr12-55697047-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BS1_Supporting

The NM_002206.3(ITGA7):​c.1589C>T​(p.Ala530Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000459 in 1,613,718 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (1 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:5
• Conservation: PhyloP100: 4.80

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2000998).
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000404 (59/1461526) while in subpopulation MID AF= 0.0014 (8/5714). AF 95% confidence interval is 0.000696. There are 1 homozygotes in gnomad4_exome. There are 38 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA7	NM_002206.3	c.1589C>T	p.Ala530Val	missense_variant	Exon 12 of 25	ENST00000257879.11	NP_002197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11	c.1589C>T	p.Ala530Val	missense_variant	Exon 12 of 25	1	NM_002206.3	ENSP00000257879.7

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000918 AC: 23 AN: 250570 Hom.: 0 AF XY: 0.000125 AC XY: 17 AN XY: 135484

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.0000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000404 AC: 59 AN: 1461526 Hom.: 1 Cov.: 33 AF XY: 0.0000523 AC XY: 38 AN XY: 727028

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000297

Gnomad4 OTH exome AF: 0.0000663

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74344

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000669 Hom.: 0

Bravo AF: 0.0000945

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000988 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital muscular dystrophy due to integrin alpha-7 deficiency Uncertain:3

Sep 11, 2019

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

May 16, 2023

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 15, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 530 of the ITGA7 protein (p.Ala530Val). This variant is present in population databases (rs200267194, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ITGA7-related conditions. ClinVar contains an entry for this variant (Variation ID: 94032). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

not provided Uncertain:2

Apr 18, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function -

May 29, 2013

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	.;.;T;.;T
Eigen	Benign	-0.079
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T;T;T;D
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	2.0	.;.;.;.;M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D
REVEL	Benign	0.068
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Benign	0.061	T;D;D;D;T
Polyphen		0.50	P;.;.;P;B
Vest4		0.33
MVP		0.38
MPC		0.55
ClinPred		0.13	T
GERP RS		3.5
Varity_R		0.068
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs200267194; hg19: chr12-56090831; COSMIC: COSV57698626; COSMIC: COSV57698626;