Variant NM_004370.6:c.7698-19_7698-15delCTTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 259346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75113758-CAAAAG-C is described in Lovd as [Likely_benign]. Variant chr6-75113758-CAAAAG-C is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

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

GnomAD3 exomes

AF:

0.0107

AC:

2214

AN:

206878

Hom.:

AF XY:

0.0108

AC XY:

1222

AN XY:

113652

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 SAS exome

AF:

0.00176

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

Gnomad4 AFR exome

AF:

0.00174

Gnomad4 AMR exome

AF:

0.00462

Gnomad4 ASJ exome

AF:

0.000441

Gnomad4 EAS exome

AF:

0.0000267

Gnomad4 SAS exome

AF:

0.00209

Gnomad4 FIN exome

AF:

0.0196

Gnomad4 NFE exome

AF:

0.0167

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.0111

AC:

1560

AN:

140206

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

759

AN XY:

68518

show subpopulations

Gnomad4 AFR

AF:

0.00271

Gnomad4 AMR

AF:

0.00655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00189

Gnomad4 FIN

AF:

0.0185

Gnomad4 NFE

AF:

0.0183

Gnomad4 OTH

AF:

0.0116

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over