rs142060614

chr12-55707637-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002206.3(ITGA7):c.46T>G(p.Cys16Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,604,662 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (8 hom., cov: 31)
  • Exomes 𝑓: 0.00064 (13 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.898

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 (MetaRNN=0.006842524).
• BP6: Variant 12-55707637-A-C is Benign according to our data. Variant chr12-55707637-A-C is described in ClinVar as [Benign]. Clinvar id is 258588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00665 (1013/152304) while in subpopulation AFR AF= 0.0228 (949/41560). AF 95% confidence interval is 0.0216. There are 8 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.46T>G	p.Cys16Gly	missense_variant	1/25	ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.46T>G	p.Cys16Gly	missense_variant	1/25	1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.00663 AC: 1009 AN: 152186 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00146 AC: 332 AN: 227896 Hom.: 1 AF XY: 0.00106 AC XY: 131 AN XY: 123644

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.000893

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000395

Gnomad OTH exome AF: 0.000887

GnomAD4 exome AF: 0.000639 AC: 928 AN: 1452358 Hom.: 13 Cov.: 31 AF XY: 0.000546 AC XY: 394 AN XY: 721584

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.00118

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000212

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000271

Gnomad4 OTH exome AF: 0.00170

GnomAD4 genome AF: 0.00665 AC: 1013 AN: 152304 Hom.: 8 Cov.: 31 AF XY: 0.00651 AC XY: 485 AN XY: 74458

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00122 Hom.: 2

Bravo AF: 0.00785

ESP6500AA AF: 0.0185 AC: 81

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00197 AC: 238

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 03, 2017	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	13
Dann	Benign	0.76
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.60	T;T;T;T
MetaRNN	Benign	0.0068	T;T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.1	M;M;.;M
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.038	D;D;D;D
Sift4G	Uncertain	0.037	D;D;D;D
Polyphen		0.010	B;.;.;.
Vest4		0.25
MVP		0.91
MPC		0.21
ClinPred		0.0042	T
GERP RS		1.9
Varity_R		0.13
gMVP		0.38

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: rs142060614; hg19: chr12-56101421; COSMIC: COSV99059711;