rs17854602

chr12-55707490-G-Cchr12-55707490-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002206.3(ITGA7):c.193C>G(p.Arg65Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R65R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028674275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA7	NM_002206.3	c.193C>G	p.Arg65Gly	missense_variant	1/25	ENST00000257879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA7	ENST00000257879.11	c.193C>G	p.Arg65Gly	missense_variant	1/25	1	NM_002206.3	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000161 AC: 4 AN: 248664 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135060

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000219

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461218 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 726918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	20
Dann	Benign	0.80
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.37	T;T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.029	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.13	N;N;.;N
MutationTaster	Benign	0.99	D;N;N;N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.26	T;T;T;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.23
MutPred		0.36		Gain of relative solvent accessibility (P = 0.0275);Gain of relative solvent accessibility (P = 0.0275);Gain of relative solvent accessibility (P = 0.0275);Gain of relative solvent accessibility (P = 0.0275);
MVP		0.42
MPC		0.21
ClinPred		0.047	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.42

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: rs17854602; hg19: chr12-56101274;