rs113651939

chr12-55693152-T-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.2701A>G(p.Ile901Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,613,798 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00097 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00075 (9 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.47

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=0.009287894).
• BP6: Variant 12-55693152-T-C is Benign according to our data. Variant chr12-55693152-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 211211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000967 (147/152002) while in subpopulation EAS AF= 0.00838 (43/5130). AF 95% confidence interval is 0.0064. There are 3 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.2701A>G	p.Ile901Val	missense_variant	20/25	ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.2701A>G	p.Ile901Val	missense_variant	20/25	1	NM_002206.3	A1

Frequencies

GnomAD3 genomes AF: 0.000909 AC: 138 AN: 151884 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000629

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00856

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00295 AC: 741 AN: 251328 Hom.: 7 AF XY: 0.00242 AC XY: 329 AN XY: 135872

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.0151

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00908

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.000752 AC: 1100 AN: 1461796 Hom.: 9 Cov.: 33 AF XY: 0.000682 AC XY: 496 AN XY: 727180

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.0130

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00728

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000594

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.000967 AC: 147 AN: 152002 Hom.: 3 Cov.: 31 AF XY: 0.000902 AC XY: 67 AN XY: 74280

Gnomad4 AFR AF: 0.000748

Gnomad4 AMR AF: 0.00367

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00838

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000551 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00256 AC: 311

Asia WGS AF: 0.0160 AC: 56 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 14, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 26, 2015	- -
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	Invitae	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 12, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	ITGA7: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 18, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	16
Dann	Uncertain	0.98
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
MetaRNN	Benign	0.0093	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.31	N;N;N;N;N
REVEL	Benign	0.021
Sift	Benign	0.22	T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T
Polyphen		0.024	B;.;.;B;B
Vest4		0.20
MVP		0.40
MPC		0.14
ClinPred		0.0047	T
GERP RS		2.6
Varity_R		0.025
gMVP		0.18

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: rs113651939; hg19: chr12-56086936;