rs149000088

Variant names:

• chr12-55701110-G-C
• rs149000088
• NM_002206.3:c.459C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-55701110-G-C
• chr12-55701110-G-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_001367994.1(ITGA7):​c.-714C>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 0.00112 in 1,614,234 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (10 hom.)
• Consequence: ITGA7 NM_001367994.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.231
• 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=0.0035514534).
• BP6: Variant 12-55701110-G-C is Benign according to our data. Variant chr12-55701110-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00616 (939/152346) while in subpopulation AFR AF = 0.0211 (879/41578). AF 95% confidence interval is 0.02. There are 8 homozygotes in GnomAd4. There are 454 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR,AD gene

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.459C>G	p.Ile153Met	missense	Exon 4 of 25	NP_002197.2	Q13683-7
	ITGA7	NM_001367994.1		c.-714C>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 24	NP_001354923.1
	ITGA7	NM_001410977.1		c.459C>G	p.Ile153Met	missense	Exon 4 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.459C>G	p.Ile153Met	missense	Exon 4 of 25	ENSP00000257879.7	Q13683-7
	ITGA7	ENST00000553804.6	TSL:1	c.459C>G	p.Ile153Met	missense	Exon 4 of 25	ENSP00000452120.1	Q13683-3
	ITGA7	ENST00000557257.2	TSL:4	c.-16C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 23	ENSP00000450578.2	G3V2C6

Frequencies

GnomAD3 genomes AF: 0.00615 AC: 936 AN: 152228 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00134 AC: 338 AN: 251382 AF XY: 0.00102

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000592 AC: 865 AN: 1461888 Hom.: 10 Cov.: 32 AF XY: 0.000517 AC XY: 376 AN XY: 727248

African (AFR) AF: 0.0202 AC: 677 AN: 33480

American (AMR) AF: 0.00116 AC: 52 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1112010

Other (OTH) AF: 0.00161 AC: 97 AN: 60396

GnomAD4 genome AF: 0.00616 AC: 939 AN: 152346 Hom.: 8 Cov.: 33 AF XY: 0.00609 AC XY: 454 AN XY: 74500

African (AFR) AF: 0.0211 AC: 879 AN: 41578

American (AMR) AF: 0.00301 AC: 46 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.000989 Hom.: 1

Bravo AF: 0.00727

ESP6500AA AF: 0.0193 AC: 85

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00186 AC: 226

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	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	0.080
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.23
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.045
Sift	Benign	0.12	T
Sift4G	Benign	0.31	T
Polyphen		0.0030	B
Vest4		0.23
MVP		0.25
MPC		0.17
ClinPred		0.0030	T
GERP RS		0.46
Varity_R		0.052
gMVP		0.41
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149000088; hg19: chr12-56094894; COSMIC: COSV99059708; COSMIC: COSV99059708;