rs201469044

Variant names:

• chr12-55698909-T-C
• rs201469044
• NM_002206.3:c.799A>G
• ITGA7 p.Ile267Val

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_001367994.1(ITGA7):​c.-494A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,611,136 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: ITGA7 NM_001367994.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5 B:1
• Conservation: PhyloP100: -0.419
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• congenital fiber-type disproportion myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009333789).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000276 (42/152022) while in subpopulation AMR AF = 0.00164 (25/15284). AF 95% confidence interval is 0.00114. There are 0 homozygotes in GnomAd4. There are 31 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367994.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	NM_002206.3	MANE Select	c.799A>G	p.Ile267Val	missense	Exon 6 of 25	NP_002197.2	Q13683-7
	ITGA7	NM_001367994.1		c.-494A>G		5_prime_UTR_premature_start_codon_gain	Exon 5 of 24	NP_001354923.1
	ITGA7	NM_001410977.1		c.931A>G	p.Ile311Val	missense	Exon 7 of 26	NP_001397906.1	Q13683-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.799A>G	p.Ile267Val	missense	Exon 6 of 25	ENSP00000257879.7	Q13683-7
	ITGA7	ENST00000553804.6	TSL:1	c.811A>G	p.Ile271Val	missense	Exon 6 of 25	ENSP00000452120.1	Q13683-3
	ITGA7	ENST00000555728.5	TSL:5	c.931A>G	p.Ile311Val	missense	Exon 7 of 26	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 151904 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000204 AC: 49 AN: 240224 AF XY: 0.000161

Gnomad AFR exome AF: 0.000469

Gnomad AMR exome AF: 0.000354

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000466

Gnomad OTH exome AF: 0.000337

GnomAD4 exome AF: 0.000110 AC: 161 AN: 1459114 Hom.: 1 Cov.: 33 AF XY: 0.000114 AC XY: 83 AN XY: 725634

African (AFR) AF: 0.00147 AC: 49 AN: 33438

American (AMR) AF: 0.000271 AC: 12 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.000443 AC: 38 AN: 85822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53002

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5764

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1110826

Other (OTH) AF: 0.000448 AC: 27 AN: 60272

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152022 Hom.: 0 Cov.: 31 AF XY: 0.000417 AC XY: 31 AN XY: 74306

African (AFR) AF: 0.000362 AC: 15 AN: 41452

American (AMR) AF: 0.00164 AC: 25 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67954

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000110 Hom.: 0

Bravo AF: 0.000431

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	3	-	Congenital muscular dystrophy due to integrin alpha-7 deficiency (3)
-	1	1	not provided (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.9
DANN	Benign	0.94
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-0.42
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.16
Sift	Benign	0.21	T
Sift4G	Benign	1.0	T
Varity_R		0.052
gMVP		0.37
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs201469044;

hg19: chr12-56092693;