12-55685088-G-A

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.3384C>T(p.Pro1128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00681 in 1,602,208 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (51 hom.)
• Consequence: ITGA7 NM_002206.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.952

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=-0.78).
• BP6: Variant 12-55685088-G-A is Benign according to our data. Variant chr12-55685088-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 129297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.952 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00488 (744/152338) while in subpopulation NFE AF= 0.00797 (542/68016). AF 95% confidence interval is 0.00741. There are 2 homozygotes in gnomad4. There are 328 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.3384C>T	p.Pro1128=	synonymous_variant	25/25	ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.3384C>T	p.Pro1128=	synonymous_variant	25/25	1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 744 AN: 152220 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00797

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00434 AC: 1047 AN: 241230 Hom.: 4 AF XY: 0.00428 AC XY: 560 AN XY: 130912

Gnomad AFR exome AF: 0.00184

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.0000550

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00607

Gnomad NFE exome AF: 0.00685

Gnomad OTH exome AF: 0.00405

GnomAD4 exome AF: 0.00701 AC: 10160 AN: 1449870 Hom.: 51 Cov.: 31 AF XY: 0.00683 AC XY: 4922 AN XY: 720658

Gnomad4 AFR exome AF: 0.00138

Gnomad4 AMR exome AF: 0.00227

Gnomad4 ASJ exome AF: 0.00280

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00157

Gnomad4 FIN exome AF: 0.00598

Gnomad4 NFE exome AF: 0.00824

Gnomad4 OTH exome AF: 0.00645

GnomAD4 genome AF: 0.00488 AC: 744 AN: 152338 Hom.: 2 Cov.: 32 AF XY: 0.00440 AC XY: 328 AN XY: 74502

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.00797

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00615 Hom.: 6

Bravo AF: 0.00454

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

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	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 20, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 17, 2013	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ITGA7: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 14, 2020	- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.26
Dann	Benign	0.86

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: rs148170949; hg19: chr12-56078872;