chr12-55695560-A-G

Variant names:

• chr12-55695560-A-G
• rs7971022
• NM_002206.3:c.1965T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002206.3(ITGA7):​c.1965T>C​(p.Cys655Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 1,612,240 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (29 hom., cov: 30)
  • Exomes 𝑓: 0.021 (402 hom.)
• Consequence: ITGA7 NM_002206.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.04
• Publications: 5 publications found

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]

ITGA7 Gene-Disease associations (from GenCC):

• congenital muscular dystrophy due to integrin alpha-7 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• congenital fiber-type disproportion myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-55695560-A-G is Benign according to our data. Variant chr12-55695560-A-G is described in ClinVar as Benign. ClinVar VariationId is 94036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.04 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0144 (2168/150850) while in subpopulation NFE AF = 0.0235 (1592/67778). AF 95% confidence interval is 0.0225. There are 29 homozygotes in GnomAd4. There are 1012 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002206.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	NM_002206.3	MANE Select	c.1965T>C	p.Cys655Cys	synonymous	Exon 14 of 25	NP_002197.2
	ITGA7	NM_001410977.1		c.2097T>C	p.Cys699Cys	synonymous	Exon 15 of 26	NP_001397906.1
	ITGA7	NM_001144996.2		c.1977T>C	p.Cys659Cys	synonymous	Exon 14 of 25	NP_001138468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.1965T>C	p.Cys655Cys	synonymous	Exon 14 of 25	ENSP00000257879.7
	ITGA7	ENST00000553804.6	TSL:1	c.1977T>C	p.Cys659Cys	synonymous	Exon 14 of 25	ENSP00000452120.1
	ITGA7	ENST00000555728.5	TSL:5	c.2097T>C	p.Cys699Cys	synonymous	Exon 15 of 26	ENSP00000452387.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2166 AN: 150736 Hom.: 29 Cov.: 30

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.00706

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0102

GnomAD2 exomes AF: 0.0162 AC: 4066 AN: 251454 AF XY: 0.0171

Gnomad AFR exome AF: 0.00308

Gnomad AMR exome AF: 0.00471

Gnomad ASJ exome AF: 0.0180

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.0234

Gnomad OTH exome AF: 0.0150

GnomAD4 exome AF: 0.0214 AC: 31306 AN: 1461390 Hom.: 402 Cov.: 33 AF XY: 0.0215 AC XY: 15596 AN XY: 727030

African (AFR) AF: 0.00341 AC: 114 AN: 33466

American (AMR) AF: 0.00543 AC: 243 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0165 AC: 431 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.0203 AC: 1755 AN: 86248

European-Finnish (FIN) AF: 0.0140 AC: 748 AN: 53388

Middle Eastern (MID) AF: 0.0114 AC: 66 AN: 5766

European-Non Finnish (NFE) AF: 0.0242 AC: 26895 AN: 1111606

Other (OTH) AF: 0.0174 AC: 1052 AN: 60370

GnomAD4 genome AF: 0.0144 AC: 2168 AN: 150850 Hom.: 29 Cov.: 30 AF XY: 0.0137 AC XY: 1012 AN XY: 73666

African (AFR) AF: 0.00396 AC: 162 AN: 40870

American (AMR) AF: 0.00705 AC: 107 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.0205 AC: 98 AN: 4784

European-Finnish (FIN) AF: 0.0119 AC: 124 AN: 10418

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0235 AC: 1592 AN: 67778

Other (OTH) AF: 0.0106 AC: 22 AN: 2080

Alfa AF: 0.0193 Hom.: 30

Bravo AF: 0.0134

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.0240

EpiControl AF: 0.0212

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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.

Mar 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Mar 31, 2020

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 10, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.6
DANN	Benign	0.57
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7971022; hg19: chr12-56089344;