rs61733963

chr12-55697019-C-Achr12-55697019-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002206.3(ITGA7):c.1617G>T(p.Gln539His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,614,096 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (65 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.321

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031561255).
• BP6: Variant 12-55697019-C-A is Benign according to our data. Variant chr12-55697019-C-A is described in ClinVar as [Benign]. Clinvar id is 129292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55697019-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.1617G>T	p.Gln539His	missense_variant	12/25	ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.1617G>T	p.Gln539His	missense_variant	12/25	1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2447 AN: 152200 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00412 AC: 1034 AN: 251208 Hom.: 35 AF XY: 0.00295 AC XY: 401 AN XY: 135812

Gnomad AFR exome AF: 0.0587

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00158 AC: 2316 AN: 1461778 Hom.: 65 Cov.: 33 AF XY: 0.00134 AC XY: 971 AN XY: 727182

Gnomad4 AFR exome AF: 0.0598

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.00320

GnomAD4 genome AF: 0.0161 AC: 2451 AN: 152318 Hom.: 60 Cov.: 32 AF XY: 0.0157 AC XY: 1169 AN XY: 74478

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00314 Hom.: 13

Bravo AF: 0.0185

ESP6500AA AF: 0.0561 AC: 247

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00528 AC: 641

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 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. -
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. -

Congenital muscular dystrophy due to integrin alpha-7 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Benign	0.12
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.74	T;T;T;T;T
MetaRNN	Benign	0.0032	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.56	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.35	B;.;.;B;B
Vest4		0.29
MutPred		0.50		.;.;.;.;Gain of methylation at R586 (P = 0.0442);
MVP		0.51
MPC		0.19
ClinPred		0.018	T
GERP RS		3.5
Varity_R		0.16
gMVP		0.62

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: rs61733963; hg19: chr12-56090803;