rs17854601

chr12-55703100-C-Achr12-55703100-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002206.3(ITGA7):c.285G>T(p.Pro95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,614,030 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P95P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.017 (28 hom., cov: 33)
  • Exomes 𝑓: 0.024 (495 hom.)
• Consequence: ITGA7 NM_002206.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.03

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 12-55703100-C-A is Benign according to our data. Variant chr12-55703100-C-A is described in ClinVar as [Benign]. Clinvar id is 129293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55703100-C-A is described in Lovd as [Likely_benign]. Variant chr12-55703100-C-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0173 (2637/152292) while in subpopulation AMR AF= 0.0278 (425/15304). AF 95% confidence interval is 0.0256. There are 28 homozygotes in gnomad4. There are 1240 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.285G>T	p.Pro95=	synonymous_variant	2/25	ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.285G>T	p.Pro95=	synonymous_variant	2/25	1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2641 AN: 152174 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.00446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0296

GnomAD3 exomes AF: 0.0186 AC: 4673 AN: 250844 Hom.: 66 AF XY: 0.0190 AC XY: 2576 AN XY: 135592

Gnomad AFR exome AF: 0.00431

Gnomad AMR exome AF: 0.0231

Gnomad ASJ exome AF: 0.0566

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00764

Gnomad FIN exome AF: 0.00293

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0279

GnomAD4 exome AF: 0.0236 AC: 34476 AN: 1461738 Hom.: 495 Cov.: 37 AF XY: 0.0234 AC XY: 16988 AN XY: 727172

Gnomad4 AFR exome AF: 0.00343

Gnomad4 AMR exome AF: 0.0233

Gnomad4 ASJ exome AF: 0.0582

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00854

Gnomad4 FIN exome AF: 0.00400

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0173 AC: 2637 AN: 152292 Hom.: 28 Cov.: 33 AF XY: 0.0167 AC XY: 1240 AN XY: 74462

Gnomad4 AFR AF: 0.00443

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00931

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0204 Hom.: 22

Bravo AF: 0.0193

EpiCase AF: 0.0299

EpiControl AF: 0.0296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 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	Athena Diagnostics	Aug 12, 2020	- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	5.9
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs17854601; hg19: chr12-56096884;