12-55697833-A-G

Variant names:

• chr12-55697833-A-G
• rs2293412
• NM_002206.3:c.1282-11T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002206.3(ITGA7):​c.1282-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,613,830 control chromosomes in the GnomAD database, including 250,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27843 hom., cov: 31)
  • Exomes 𝑓: 0.54 (222606 hom.)
• Consequence: ITGA7 NM_002206.3 intron
• Scores: Splicing: ADA: 0.004115
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0950
• Publications: 12 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 (BayesDel_noAF=-0.86).
• BP6: Variant 12-55697833-A-G is Benign according to our data. Variant chr12-55697833-A-G is described in ClinVar as Benign. ClinVar VariationId is 94031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

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.1282-11T>C		intron	N/A	NP_002197.2	Q13683-7
	ITGA7	NM_001410977.1		c.1414-11T>C		intron	N/A	NP_001397906.1	Q13683-1
	ITGA7	NM_001144996.2		c.1294-11T>C		intron	N/A	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.1282-11T>C		intron	N/A	ENSP00000257879.7	Q13683-7
	ITGA7	ENST00000553804.6	TSL:1	c.1294-11T>C		intron	N/A	ENSP00000452120.1	Q13683-3
	ITGA7	ENST00000555728.5	TSL:5	c.1414-11T>C		intron	N/A	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90619 AN: 151864 Hom.: 27801 Cov.: 31

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.557

GnomAD2 exomes AF: 0.623 AC: 156584 AN: 251448 AF XY: 0.617

Gnomad AFR exome AF: 0.663

Gnomad AMR exome AF: 0.749

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.948

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.516

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.542 AC: 792936 AN: 1461850 Hom.: 222606 Cov.: 70 AF XY: 0.546 AC XY: 396979 AN XY: 727238

African (AFR) AF: 0.653 AC: 21878 AN: 33480

American (AMR) AF: 0.736 AC: 32938 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 12524 AN: 26136

East Asian (EAS) AF: 0.942 AC: 37399 AN: 39700

South Asian (SAS) AF: 0.695 AC: 59912 AN: 86258

European-Finnish (FIN) AF: 0.642 AC: 34308 AN: 53420

Middle Eastern (MID) AF: 0.538 AC: 3105 AN: 5768

European-Non Finnish (NFE) AF: 0.501 AC: 557282 AN: 1111968

Other (OTH) AF: 0.556 AC: 33590 AN: 60396

GnomAD4 genome AF: 0.597 AC: 90719 AN: 151980 Hom.: 27843 Cov.: 31 AF XY: 0.608 AC XY: 45144 AN XY: 74304

African (AFR) AF: 0.657 AC: 27244 AN: 41436

American (AMR) AF: 0.645 AC: 9854 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3466

East Asian (EAS) AF: 0.943 AC: 4869 AN: 5162

South Asian (SAS) AF: 0.718 AC: 3460 AN: 4818

European-Finnish (FIN) AF: 0.653 AC: 6901 AN: 10576

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34892 AN: 67934

Other (OTH) AF: 0.562 AC: 1185 AN: 2108

Alfa AF: 0.520 Hom.: 5770

Bravo AF: 0.597

Asia WGS AF: 0.803 AC: 2791 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0041
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: rs2293412; hg19: chr12-56091617; COSMIC: COSV57691137; COSMIC: COSV57691137;