Genetic Variant COL12A1:c.9181+295delT (chr6-75087281-GA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_004370.6(COL12A1):c.9181+295delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.98 ( 72146 hom., cov: 0)

Exomes 𝑓: 0.90 ( 62277 hom. )

Consequence

COL12A1
NM_004370.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.554

Publications

0 publications found

Variant links:

Genes affected

COL12A1 (HGNC:2188): (collagen type XII alpha 1 chain) This gene encodes the alpha chain of type XII collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XII collagen is a homotrimer found in association with type I collagen, an association that is thought to modify the interactions between collagen I fibrils and the surrounding matrix. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

COL12A1 Gene-Disease associations (from GenCC):

Bethlem myopathy 2
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
Bethlem myopathy 2
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Illumina, Genomics England PanelApp
Ullrich congenital muscular dystrophy 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Bethlem myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ullrich congenital muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL12A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 6-75087281-GA-G is Benign according to our data. Variant chr6-75087281-GA-G is described in ClinVar as [Benign]. Clinvar id is 1262224.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL12A1	NM_004370.6 link	c.9181+295delT		intron_variant	Intron 65 of 65	ENST00000322507.13	NP_004361.3	Q99715-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13 link	c.9181+295delT		intron_variant	Intron 65 of 65	1	NM_004370.6	ENSP00000325146.8		Q99715-1

Frequencies

GnomAD3 genomes

AF:

0.978

AC:

147405

AN:

150698

Hom.:

72095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.993

Gnomad AMI

AF:

0.962

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

0.972

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.974

Gnomad FIN

AF:

0.964

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.969

Gnomad OTH

AF:

0.971

GnomAD4 exome

AF:

0.902

AC:

139426

AN:

154574

Hom.:

62277

Cov.:

AF XY:

0.901

AC XY:

70492

AN XY:

78266

show subpopulations

African (AFR)

AF:

0.934

AC:

4270

AN:

4572

American (AMR)

AF:

0.920

AC:

4801

AN:

5220

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

5334

AN:

5884

East Asian (EAS)

AF:

0.938

AC:

12285

AN:

13104

South Asian (SAS)

AF:

0.875

AC:

2916

AN:

3332

European-Finnish (FIN)

AF:

0.894

AC:

9841

AN:

11008

Middle Eastern (MID)

AF:

0.889

AC:

750

AN:

844

European-Non Finnish (NFE)

AF:

0.896

AC:

89723

AN:

100086

Other (OTH)

AF:

0.903

AC:

9506

AN:

10524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.685

Heterozygous variant carriers

1179

2359

3538

4718

5897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.978

AC:

147508

AN:

150802

Hom.:

72146

Cov.:

AF XY:

0.979

AC XY:

72018

AN XY:

73592

show subpopulations

African (AFR)

AF:

0.993

AC:

40812

AN:

41102

American (AMR)

AF:

0.985

AC:

14935

AN:

15162

Ashkenazi Jewish (ASJ)

AF:

0.972

AC:

3359

AN:

3456

East Asian (EAS)

AF:

0.999

AC:

5136

AN:

5142

South Asian (SAS)

AF:

0.974

AC:

4642

AN:

4764

European-Finnish (FIN)

AF:

0.964

AC:

9834

AN:

10198

Middle Eastern (MID)

AF:

0.980

AC:

288

AN:

294

European-Non Finnish (NFE)

AF:

0.969

AC:

65598

AN:

67686

Other (OTH)

AF:

0.971

AC:

2032

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

161

322

482

643

804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.962

Hom.:

1977

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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6-75087281-GAAA-GAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over