rs11171663

chr12-55712110-G-A

Variant summary

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

The NM_001144997.2(ITGA7):c.38C>T(p.Thr13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,551,446 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (15 hom., cov: 33)
  • Exomes 𝑓: 0.012 (138 hom.)
• Consequence: ITGA7 NM_001144997.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.21

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=0.0033804476).
• BP6: Variant 12-55712110-G-A is Benign according to our data. Variant chr12-55712110-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 586038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55712110-G-A is described in Lovd as [Benign]. Variant chr12-55712110-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00922 (1404/152330) while in subpopulation NFE AF= 0.0155 (1054/68028). AF 95% confidence interval is 0.0147. There are 15 homozygotes in gnomad4. There are 645 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_001144997.2	c.38C>T	p.Thr13Ile	missense_variant	2/25
ITGA7	NM_001367993.1	c.-181C>T		5_prime_UTR_variant	2/26
ITGA7	NM_001414035.1	c.-181C>T		5_prime_UTR_variant	1/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000452168.6	c.38C>T	p.Thr13Ile	missense_variant	2/25	2
ITGA7	ENST00000557257.2	c.-108C>T		5_prime_UTR_variant	1/23	4
ITGA7	ENST00000553276.1	n.95C>T		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.00924 AC: 1406 AN: 152212 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00941

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00861 AC: 1325 AN: 153832 Hom.: 7 AF XY: 0.00882 AC XY: 720 AN XY: 81612

Gnomad AFR exome AF: 0.00290

Gnomad AMR exome AF: 0.00506

Gnomad ASJ exome AF: 0.00553

Gnomad EAS exome AF: 0.000183

Gnomad SAS exome AF: 0.00426

Gnomad FIN exome AF: 0.00910

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.00577

GnomAD4 exome AF: 0.0123 AC: 17207 AN: 1399116 Hom.: 138 Cov.: 31 AF XY: 0.0122 AC XY: 8445 AN XY: 690076

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00560

Gnomad4 ASJ exome AF: 0.00552

Gnomad4 EAS exome AF: 0.0000839

Gnomad4 SAS exome AF: 0.00464

Gnomad4 FIN exome AF: 0.00992

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.00922 AC: 1404 AN: 152330 Hom.: 15 Cov.: 33 AF XY: 0.00866 AC XY: 645 AN XY: 74496

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00941

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.0133 Hom.: 26

Bravo AF: 0.00858

TwinsUK AF: 0.0143 AC: 53

ALSPAC AF: 0.0130 AC: 50

ESP6500AA AF: 0.00289 AC: 4

ESP6500EA AF: 0.00943 AC: 30

ExAC AF: 0.00654 AC: 155

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 23, 2020	- -

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	15
Dann	Uncertain	1.0
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.064
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0080	B
Vest4		0.10
MVP		0.30
ClinPred		0.017	T
GERP RS		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11171663; hg19: chr12-56105894; COSMIC: COSV57702037; COSMIC: COSV57702037;