rs3852533

Variant names:

• chr12-55685300-C-G
• rs3852533
• NM_002206.3:c.3184-12G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-55685300-C-G
• chr12-55685300-C-A
• chr12-55685300-C-T

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.3184-12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,612,502 control chromosomes in the GnomAD database, including 231,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19996 hom., cov: 33)
  • Exomes 𝑓: 0.53 (211853 hom.)
• Consequence: ITGA7 NM_002206.3 intron
• Scores: Splicing: ADA: 0.00005187
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.736
• Publications: 13 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=-0.82).
• BP6: Variant 12-55685300-C-G is Benign according to our data. Variant chr12-55685300-C-G is described in ClinVar as Benign. ClinVar VariationId is 94043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 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.3184-12G>C		intron	N/A	NP_002197.2	Q13683-7
	ITGA7	NM_001410977.1		c.3316-12G>C		intron	N/A	NP_001397906.1	Q13683-1
	ITGA7	NM_001144996.2		c.3196-12G>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.3184-12G>C		intron	N/A	ENSP00000257879.7	Q13683-7
	ITGA7	ENST00000553804.6	TSL:1	c.3196-12G>C		intron	N/A	ENSP00000452120.1	Q13683-3
	ITGA7	ENST00000555728.5	TSL:5	c.3316-12G>C		intron	N/A	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74629 AN: 152044 Hom.: 19985 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.591 AC: 148000 AN: 250454 AF XY: 0.593

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.528 AC: 771012 AN: 1460340 Hom.: 211853 Cov.: 35 AF XY: 0.533 AC XY: 387447 AN XY: 726536

African (AFR) AF: 0.283 AC: 9475 AN: 33456

American (AMR) AF: 0.701 AC: 31331 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 12131 AN: 26134

East Asian (EAS) AF: 0.935 AC: 37106 AN: 39698

South Asian (SAS) AF: 0.703 AC: 60598 AN: 86232

European-Finnish (FIN) AF: 0.640 AC: 33842 AN: 52900

Middle Eastern (MID) AF: 0.500 AC: 2885 AN: 5766

European-Non Finnish (NFE) AF: 0.497 AC: 551740 AN: 1111088

Other (OTH) AF: 0.529 AC: 31904 AN: 60354

GnomAD4 genome AF: 0.491 AC: 74667 AN: 152162 Hom.: 19996 Cov.: 33 AF XY: 0.506 AC XY: 37614 AN XY: 74394

African (AFR) AF: 0.299 AC: 12417 AN: 41526

American (AMR) AF: 0.602 AC: 9218 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3470

East Asian (EAS) AF: 0.935 AC: 4823 AN: 5156

South Asian (SAS) AF: 0.724 AC: 3493 AN: 4826

European-Finnish (FIN) AF: 0.651 AC: 6901 AN: 10604

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34543 AN: 67960

Other (OTH) AF: 0.480 AC: 1014 AN: 2112

Alfa AF: 0.487 Hom.: 3354

Bravo AF: 0.474

Asia WGS AF: 0.770 AC: 2674 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	-0.82
CADD	Benign	6.3
DANN	Benign	0.65
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000052
dbscSNV1_RF	Benign	0.038
SpliceAI score (max)		0.010		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: rs3852533; hg19: chr12-56079084;