chr12-55701032-C-T

Position:

• chr12-55701032-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The ENST00000257879.11(ITGA7):​c.537G>A​(p.Gly179=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000817 in 1,614,236 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (3 hom.)
• Consequence: ITGA7 ENST00000257879.11 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -1.30

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 12-55701032-C-T is Benign according to our data. Variant chr12-55701032-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 287417.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}. Variant chr12-55701032-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.3 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000832 (1217/1461894) while in subpopulation MID AF= 0.00416 (24/5768). AF 95% confidence interval is 0.00287. There are 3 homozygotes in gnomad4_exome. There are 633 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA7	NM_002206.3	c.537G>A	p.Gly179=	synonymous_variant	4/25	ENST00000257879.11	NP_002197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11	c.537G>A	p.Gly179=	synonymous_variant	4/25	1	NM_002206.3	ENSP00000257879	A1

Frequencies

GnomAD3 genomes AF: 0.000670 AC: 102 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000756 AC: 190 AN: 251476 Hom.: 0 AF XY: 0.000736 AC XY: 100 AN XY: 135916

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000686

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00117

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000832 AC: 1217 AN: 1461894 Hom.: 3 Cov.: 32 AF XY: 0.000870 AC XY: 633 AN XY: 727248

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000614

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000924

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.000670 AC: 102 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.000725 AC XY: 54 AN XY: 74498

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000970

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000732 Hom.: 0

Bravo AF: 0.000661

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00101

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	ITGA7: BP4, BP7 -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 15, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2020	- -

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs145463677; hg19: chr12-56094816;