rs17117883

chr12-55688241-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002206.3(ITGA7):c.3018C>G(p.Ser1006=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 1,613,858 control chromosomes in the GnomAD database, including 2,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (217 hom., cov: 31)
  • Exomes 𝑓: 0.049 (1957 hom.)
• Consequence: ITGA7 NM_002206.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.997

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=-0.61).
• BP6: Variant 12-55688241-G-C is Benign according to our data. Variant chr12-55688241-G-C is described in ClinVar as [Benign]. Clinvar id is 129294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55688241-G-C is described in Lovd as [Benign]. Variant chr12-55688241-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.997 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.3018C>G	p.Ser1006=	synonymous_variant	23/25	ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.3018C>G	p.Ser1006=	synonymous_variant	23/25	1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7542 AN: 152096 Hom.: 215 Cov.: 31

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0575

GnomAD3 exomes AF: 0.0410 AC: 10297 AN: 251448 Hom.: 277 AF XY: 0.0428 AC XY: 5812 AN XY: 135902

Gnomad AFR exome AF: 0.0641

Gnomad AMR exome AF: 0.0227

Gnomad ASJ exome AF: 0.0414

Gnomad EAS exome AF: 0.00141

Gnomad SAS exome AF: 0.0534

Gnomad FIN exome AF: 0.0228

Gnomad NFE exome AF: 0.0495

Gnomad OTH exome AF: 0.0443

GnomAD4 exome AF: 0.0489 AC: 71483 AN: 1461644 Hom.: 1957 Cov.: 33 AF XY: 0.0495 AC XY: 35981 AN XY: 727152

Gnomad4 AFR exome AF: 0.0633

Gnomad4 AMR exome AF: 0.0249

Gnomad4 ASJ exome AF: 0.0382

Gnomad4 EAS exome AF: 0.000831

Gnomad4 SAS exome AF: 0.0536

Gnomad4 FIN exome AF: 0.0218

Gnomad4 NFE exome AF: 0.0522

Gnomad4 OTH exome AF: 0.0481

GnomAD4 genome AF: 0.0496 AC: 7550 AN: 152214 Hom.: 217 Cov.: 31 AF XY: 0.0478 AC XY: 3561 AN XY: 74422

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.0420

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0569

Alfa AF: 0.0518 Hom.: 68

Bravo AF: 0.0499

Asia WGS AF: 0.0240 AC: 83 AN: 3478

EpiCase AF: 0.0541

EpiControl AF: 0.0528

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 08, 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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 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. -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	4.7
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: rs17117883; hg19: chr12-56082025; COSMIC: COSV57702510; COSMIC: COSV57702510;