rs773251917

chr12-55697548-TG-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002206.3(ITGA7):c.1410-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,613,590 control chromosomes in the GnomAD database, including 31 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (25 hom.)
• Consequence: ITGA7 NM_002206.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.188

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 -16 ACMG points.

• BP6: Variant 12-55697548-TG-T is Benign according to our data. Variant chr12-55697548-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 193638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00345 (525/152248) while in subpopulation NFE AF= 0.00604 (411/67992). AF 95% confidence interval is 0.00556. There are 6 homozygotes in gnomad4. There are 244 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.1410-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.1410-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 524 AN: 152130 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00698

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00603

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00285 AC: 716 AN: 251162 Hom.: 4 AF XY: 0.00300 AC XY: 407 AN XY: 135770

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00593

Gnomad NFE exome AF: 0.00491

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00231 AC: 3372 AN: 1461342 Hom.: 25 Cov.: 32 AF XY: 0.00244 AC XY: 1773 AN XY: 726990

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00536

Gnomad4 NFE exome AF: 0.00263

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.00345 AC: 525 AN: 152248 Hom.: 6 Cov.: 32 AF XY: 0.00328 AC XY: 244 AN XY: 74440

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00698

Gnomad4 NFE AF: 0.00604

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00750 Hom.: 3

Bravo AF: 0.00203

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00308

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 04, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 09, 2018	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	Eurofins Ntd Llc (ga)	Mar 25, 2015	- -

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

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 08, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

ITGA7-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 05, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

ITGA7: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs773251917; hg19: chr12-56091332;