rs150583010

Variant names:

• chr12-55696342-C-T
• rs150583010
• NM_002206.3:c.1828G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002206.3(ITGA7):​c.1828G>A​(p.Gly610Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00067 in 1,586,216 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G610V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00085 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (9 hom.)
• Consequence: ITGA7 NM_002206.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.180
• 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, Orphanet, Labcorp Genetics (formerly Invitae)
• congenital fiber-type disproportion myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004872501).
• BP6: Variant 12-55696342-C-T is Benign according to our data. Variant chr12-55696342-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 284004.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 = 0.000847 (129/152304) while in subpopulation EAS AF = 0.00772 (40/5178). AF 95% confidence interval is 0.00583. There are 3 homozygotes in GnomAd4. There are 56 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	NM_002206.3	MANE Select	c.1828G>A	p.Gly610Arg	missense	Exon 13 of 25	NP_002197.2	Q13683-7
	ITGA7	NM_001410977.1		c.1960G>A	p.Gly654Arg	missense	Exon 14 of 26	NP_001397906.1	Q13683-1
	ITGA7	NM_001144996.2		c.1840G>A	p.Gly614Arg	missense	Exon 13 of 25	NP_001138468.1	Q13683-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.1828G>A	p.Gly610Arg	missense	Exon 13 of 25	ENSP00000257879.7	Q13683-7
	ITGA7	ENST00000553804.6	TSL:1	c.1840G>A	p.Gly614Arg	missense	Exon 13 of 25	ENSP00000452120.1	Q13683-3
	ITGA7	ENST00000555728.5	TSL:5	c.1960G>A	p.Gly654Arg	missense	Exon 14 of 26	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 125 AN: 152186 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00298 AC: 610 AN: 204652 AF XY: 0.00249

Gnomad AFR exome AF: 0.000157

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.000327

Gnomad EAS exome AF: 0.00848

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000913

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.000651 AC: 933 AN: 1433912 Hom.: 9 Cov.: 35 AF XY: 0.000594 AC XY: 422 AN XY: 710690

African (AFR) AF: 0.0000604 AC: 2 AN: 33104

American (AMR) AF: 0.0124 AC: 508 AN: 40914

Ashkenazi Jewish (ASJ) AF: 0.000156 AC: 4 AN: 25572

East Asian (EAS) AF: 0.00698 AC: 270 AN: 38688

South Asian (SAS) AF: 0.000255 AC: 21 AN: 82374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.0000538 AC: 59 AN: 1097204

Other (OTH) AF: 0.00116 AC: 69 AN: 59236

GnomAD4 genome AF: 0.000847 AC: 129 AN: 152304 Hom.: 3 Cov.: 32 AF XY: 0.000752 AC XY: 56 AN XY: 74466

African (AFR) AF: 0.000313 AC: 13 AN: 41568

American (AMR) AF: 0.00386 AC: 59 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000488 Hom.: 0

Bravo AF: 0.00156

ExAC AF: 0.00210 AC: 254

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.18
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.036
Sift	Benign	0.39	T
Sift4G	Benign	0.51	T
Polyphen		0.010	B
Vest4		0.27
MutPred		0.39		Gain of solvent accessibility (P = 0.0097)
MVP		0.38
MPC		0.36
ClinPred		0.016	T
GERP RS		3.9
Varity_R		0.075
gMVP		0.36
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs150583010; hg19: chr12-56090126; COSMIC: COSV57697469; COSMIC: COSV57697469;