12-55685300-C-G

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.3184-12G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,612,502 control chromosomes in the GnomAD database, including 231,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19996 hom., cov: 33)
  • Exomes 𝑓: 0.53 (211853 hom.)
• Consequence: ITGA7 NM_002206.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005187
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.736

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=-0.82).
• BP6: Variant 12-55685300-C-G is Benign according to our data. Variant chr12-55685300-C-G is described in ClinVar as [Benign]. Clinvar id is 94043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55685300-C-G 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.3184-12G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.3184-12G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74629 AN: 152044 Hom.: 19985 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.476

GnomAD3 exomes AF: 0.591 AC: 148000 AN: 250454 Hom.: 46718 AF XY: 0.593 AC XY: 80351 AN XY: 135414

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.939

Gnomad SAS exome AF: 0.708

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.528 AC: 771012 AN: 1460340 Hom.: 211853 Cov.: 35 AF XY: 0.533 AC XY: 387447 AN XY: 726536

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.701

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.935

Gnomad4 SAS exome AF: 0.703

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.491 AC: 74667 AN: 152162 Hom.: 19996 Cov.: 33 AF XY: 0.506 AC XY: 37614 AN XY: 74394

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.935

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.480

Alfa AF: 0.487 Hom.: 3354

Bravo AF: 0.474

Asia WGS AF: 0.770 AC: 2674 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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 18, 2012	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 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. -

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	-0.82
Cadd	Benign	6.3
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000052
dbscSNV1_RF	Benign	0.038
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: rs3852533; hg19: chr12-56079084;