12-55697833-A-G

Position:

• chr12-55697833-A-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.1282-11T>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 0.548 in 1,613,830 control chromosomes in the GnomAD database, including 250,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27843 hom., cov: 31)
  • Exomes 𝑓: 0.54 (222606 hom.)
• Consequence: ITGA7 NM_002206.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.004115
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0950

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 12-55697833-A-G is Benign according to our data. Variant chr12-55697833-A-G is described in ClinVar as [Benign]. Clinvar id is 94031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55697833-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.1282-11T>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.1282-11T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90619 AN: 151864 Hom.: 27801 Cov.: 31

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.557

GnomAD3 exomes AF: 0.623 AC: 156584 AN: 251448 Hom.: 51135 AF XY: 0.617 AC XY: 83816 AN XY: 135906

Gnomad AFR exome AF: 0.663

Gnomad AMR exome AF: 0.749

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.948

Gnomad SAS exome AF: 0.699

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.516

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.542 AC: 792936 AN: 1461850 Hom.: 222606 Cov.: 70 AF XY: 0.546 AC XY: 396979 AN XY: 727238

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.736

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.942

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.597 AC: 90719 AN: 151980 Hom.: 27843 Cov.: 31 AF XY: 0.608 AC XY: 45144 AN XY: 74304

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.562

Alfa AF: 0.517 Hom.: 5596

Bravo AF: 0.597

Asia WGS AF: 0.803 AC: 2791 AN: 3478

ClinVar

Significance: 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	GeneDx	Jan 05, 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)	Jul 18, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
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	1.3
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0041
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: rs2293412; hg19: chr12-56091617; COSMIC: COSV57691137; COSMIC: COSV57691137;