Variant rs9447445 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004370.6(COL12A1):c.8265+19A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 1,596,606 control chromosomes in the GnomAD database, including 4,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2029 hom., cov: 32)

Exomes 𝑓: 0.033 ( 2819 hom. )

Consequence

COL12A1
NM_004370.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0960

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-75105187-T-A is Benign according to our data. Variant chr6-75105187-T-A is described in ClinVar as [Benign]. Clinvar id is 259350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75105187-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL12A1	NM_004370.6 linkuse as main transcript	c.8265+19A>T		intron_variant		ENST00000322507.13	NP_004361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13 linkuse as main transcript	c.8265+19A>T		intron_variant		1	NM_004370.6	ENSP00000325146	P4	Q99715-1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16509

AN:

152052

Hom.:

2016

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0835

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0522

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0923

GnomAD3 exomes

AF:

0.0629

AC:

15437

AN:

245468

Hom.:

1330

AF XY:

0.0562

AC XY:

7491

AN XY:

133184

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.0741

Gnomad ASJ exome

AF:

0.0542

Gnomad EAS exome

AF:

0.202

Gnomad SAS exome

AF:

0.0459

Gnomad FIN exome

AF:

0.0159

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0481

GnomAD4 exome

AF:

0.0326

AC:

47117

AN:

1444436

Hom.:

2819

Cov.:

AF XY:

0.0321

AC XY:

23124

AN XY:

719582

show subpopulations

Gnomad4 AFR exome

AF:

0.312

Gnomad4 AMR exome

AF:

0.0736

Gnomad4 ASJ exome

AF:

0.0518

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.0463

Gnomad4 FIN exome

AF:

0.0163

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0536

GnomAD4 genome

AF:

0.109

AC:

16553

AN:

152170

Hom.:

2029

Cov.:

AF XY:

0.108

AC XY:

8054

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.0836

Gnomad4 ASJ

AF:

0.0412

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.0512

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0928

Alfa

AF:

0.0612

Hom.:

164

Bravo

AF:

0.123

Asia WGS

AF:

0.132

AC:

458

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.65

DANN

Benign

0.39

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

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