rs11171661

Positions:

• chr12-55701164-G-A

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.415-10C>T 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 0.0849 in 1,613,994 control chromosomes in the GnomAD database, including 6,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (444 hom., cov: 33)
  • Exomes 𝑓: 0.087 (6320 hom.)
• Consequence: ITGA7 NM_002206.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001970
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.35

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=-0.86).
• BP6: Variant 12-55701164-G-A is Benign according to our data. Variant chr12-55701164-G-A is described in ClinVar as [Benign]. Clinvar id is 94045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55701164-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA7	NM_002206.3	c.415-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000257879.11	NP_002197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11	c.415-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002206.3	ENSP00000257879	A1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9593 AN: 152176 Hom.: 444 Cov.: 33

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0684

GnomAD3 exomes AF: 0.0627 AC: 15748 AN: 251000 Hom.: 705 AF XY: 0.0626 AC XY: 8500 AN XY: 135732

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.0386

Gnomad ASJ exome AF: 0.0491

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0176

Gnomad FIN exome AF: 0.0643

Gnomad NFE exome AF: 0.0994

Gnomad OTH exome AF: 0.0721

GnomAD4 exome AF: 0.0872 AC: 127496 AN: 1461700 Hom.: 6320 Cov.: 33 AF XY: 0.0854 AC XY: 62102 AN XY: 727172

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.0408

Gnomad4 ASJ exome AF: 0.0493

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0185

Gnomad4 FIN exome AF: 0.0700

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0775

GnomAD4 genome AF: 0.0629 AC: 9585 AN: 152294 Hom.: 444 Cov.: 33 AF XY: 0.0609 AC XY: 4534 AN XY: 74476

Gnomad4 AFR AF: 0.0166

Gnomad4 AMR AF: 0.0548

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0655

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0756 Hom.: 144

Bravo AF: 0.0603

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 26, 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	Eurofins Ntd Llc (ga)	Sep 20, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 31, 2021	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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: rs11171661; hg19: chr12-56094948;