12-55703032-T-C

Position:

• chr12-55703032-T-C

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.334+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,613,676 control chromosomes in the GnomAD database, including 235,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20973 hom., cov: 33)
  • Exomes 𝑓: 0.53 (214398 hom.)
• Consequence: ITGA7 NM_002206.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.642

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 (BayesDel_noAF=-0.94).
• BP6: Variant 12-55703032-T-C is Benign according to our data. Variant chr12-55703032-T-C is described in ClinVar as [Benign]. Clinvar id is 94044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55703032-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.334+19A>G		intron_variant		ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.334+19A>G		intron_variant		1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77558 AN: 151962 Hom.: 20959 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.490

GnomAD3 exomes AF: 0.596 AC: 149770 AN: 251112 Hom.: 47349 AF XY: 0.597 AC XY: 81032 AN XY: 135736

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.716

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.939

Gnomad SAS exome AF: 0.701

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.513

Gnomad OTH exome AF: 0.553

GnomAD4 exome AF: 0.532 AC: 777442 AN: 1461596 Hom.: 214398 Cov.: 57 AF XY: 0.537 AC XY: 390214 AN XY: 727110

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.703

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.936

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.641

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.533

GnomAD4 genome AF: 0.510 AC: 77605 AN: 152080 Hom.: 20973 Cov.: 33 AF XY: 0.524 AC XY: 38956 AN XY: 74324

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.935

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.494

Alfa AF: 0.435 Hom.: 2574

Bravo AF: 0.497

Asia WGS AF: 0.768 AC: 2668 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 18, 2012	- -

Congenital muscular dystrophy due to integrin alpha-7 deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2293413; hg19: chr12-56096816;