rs141102808

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004370.6(COL12A1):c.7698-19_7698-15delCTTTT variant causes a intron change. The variant allele was found at a frequency of 0.0141 in 1,500,544 control chromosomes in the GnomAD database, including 165 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 10 hom., cov: 32)

Exomes 𝑓: 0.014 ( 155 hom. )

Consequence

COL12A1
NM_004370.6 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.65

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 -16 ACMG points.

BP6

Variant 6-75113758-CAAAAG-C is Benign according to our data. Variant chr6-75113758-CAAAAG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0111 (1560/140206) while in subpopulation NFE AF = 0.0183 (1148/62890). AF 95% confidence interval is 0.0174. There are 10 homozygotes in GnomAd4. There are 759 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL12A1	NM_004370.6 link	c.7698-19_7698-15delCTTTT		intron_variant	Intron 49 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.7698-19_7698-15delCTTTT		intron_variant	Intron 49 of 65	1	NM_004370.6	ENSP00000325146.8		Q99715-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1560

AN:

140082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00272

Gnomad AMI

AF:

0.00239

Gnomad AMR

AF:

0.00656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00188

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.00355

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.0117

GnomAD2 exomes

AF:

0.0107

AC:

2214

AN:

206878

AF XY:

0.0108

show subpopulations

Gnomad AFR exome

AF:

0.00262

Gnomad AMR exome

AF:

0.00481

Gnomad ASJ exome

AF:

0.000390

Gnomad EAS exome

AF:

0.0000693

Gnomad FIN exome

AF:

0.0174

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0145

AC:

19657

AN:

1360338

Hom.:

155

AF XY:

0.0141

AC XY:

9538

AN XY:

674160

show subpopulations

African (AFR)

AF:

0.00174

AC:

AN:

29892

American (AMR)

AF:

0.00462

AC:

157

AN:

33984

Ashkenazi Jewish (ASJ)

AF:

0.000441

AC:

AN:

22678

East Asian (EAS)

AF:

0.0000267

AC:

AN:

37518

South Asian (SAS)

AF:

0.00209

AC:

142

AN:

67806

European-Finnish (FIN)

AF:

0.0196

AC:

971

AN:

49464

Middle Eastern (MID)

AF:

0.00151

AC:

AN:

5308

European-Non Finnish (NFE)

AF:

0.0167

AC:

17633

AN:

1058200

Other (OTH)

AF:

0.0123

AC:

683

AN:

55488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

775

1550

2325

3100

3875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0111

AC:

1560

AN:

140206

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

759

AN XY:

68518

show subpopulations

African (AFR)

AF:

0.00271

AC:

103

AN:

38048

American (AMR)

AF:

0.00655

AC:

AN:

14208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3238

East Asian (EAS)

AF:

0.00

AC:

AN:

4688

South Asian (SAS)

AF:

0.00189

AC:

AN:

4244

European-Finnish (FIN)

AF:

0.0185

AC:

183

AN:

9888

Middle Eastern (MID)

AF:

0.00379

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0183

AC:

1148

AN:

62890

Other (OTH)

AF:

0.0116

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0137

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 22, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.6

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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