rs79745402

Variant names:

• chr12-55694128-C-T
• rs79745402
• NM_002206.3:c.2433-5G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-55694128-C-T
• chr12-55694128-C-A

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.2433-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,613,934 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (65 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (88 hom.)
• Consequence: ITGA7 NM_002206.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006498
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.41
• 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: 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=-0.93).
• BP6: Variant 12-55694128-C-T is Benign according to our data. Variant chr12-55694128-C-T is described in ClinVar as Benign. ClinVar VariationId is 94039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 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.2433-5G>A		splice_region intron	N/A	NP_002197.2	Q13683-7
	ITGA7	NM_001410977.1		c.2565-5G>A		splice_region intron	N/A	NP_001397906.1	Q13683-1
	ITGA7	NM_001144996.2		c.2445-5G>A		splice_region 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.2433-5G>A		splice_region intron	N/A	ENSP00000257879.7	Q13683-7
	ITGA7	ENST00000553804.6	TSL:1	c.2445-5G>A		splice_region intron	N/A	ENSP00000452120.1	Q13683-3
	ITGA7	ENST00000555728.5	TSL:5	c.2565-5G>A		splice_region intron	N/A	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2926 AN: 152210 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00742 AC: 1864 AN: 251280 AF XY: 0.00627

Gnomad AFR exome AF: 0.0595

Gnomad AMR exome AF: 0.00564

Gnomad ASJ exome AF: 0.0163

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00403

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00639 AC: 9337 AN: 1461606 Hom.: 88 Cov.: 32 AF XY: 0.00605 AC XY: 4400 AN XY: 727142

African (AFR) AF: 0.0607 AC: 2031 AN: 33472

American (AMR) AF: 0.00555 AC: 248 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0157 AC: 410 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000939 AC: 81 AN: 86254

European-Finnish (FIN) AF: 0.000805 AC: 43 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00539 AC: 5997 AN: 1111758

Other (OTH) AF: 0.00861 AC: 520 AN: 60378

GnomAD4 genome AF: 0.0192 AC: 2930 AN: 152328 Hom.: 65 Cov.: 32 AF XY: 0.0185 AC XY: 1381 AN XY: 74490

African (AFR) AF: 0.0572 AC: 2377 AN: 41564

American (AMR) AF: 0.0109 AC: 167 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4834

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00426 AC: 290 AN: 68030

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.0145 Hom.: 39

Bravo AF: 0.0222

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00463

EpiControl AF: 0.00451

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Congenital muscular dystrophy due to integrin alpha-7 deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0080
DANN	Benign	0.45
PhyloP100		-3.4
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.046
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: rs79745402; hg19: chr12-56087912;