Variant rs60109744 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_004370.6(COL12A1):c.1892-6A>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,258,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

COL12A1
NM_004370.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.000006899

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.52

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-75181217-T-A is Benign according to our data. Variant chr6-75181217-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 259321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL12A1	NM_004370.6 linkuse as main transcript	c.1892-6A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000322507.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL12A1	ENST00000322507.13 linkuse as main transcript	c.1892-6A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004370.6	P4	Q99715-1

Frequencies

GnomAD3 genomes

AF:

0.0000682

AC:

AN:

146658

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000600

Gnomad OTH

AF:

0.000497

GnomAD3 exomes

AF:

0.000537

AC:

AN:

143334

Hom.:

AF XY:

0.000406

AC XY:

AN XY:

78814

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.000937

Gnomad EAS exome

AF:

0.000920

Gnomad SAS exome

AF:

0.000171

Gnomad FIN exome

AF:

0.000928

Gnomad NFE exome

AF:

0.000519

Gnomad OTH exome

AF:

0.000300

GnomAD4 exome

AF:

0.000311

AC:

346

AN:

1111988

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

181

AN XY:

552678

show subpopulations

Gnomad4 AFR exome

AF:

0.000221

Gnomad4 AMR exome

AF:

0.000474

Gnomad4 ASJ exome

AF:

0.000302

Gnomad4 EAS exome

AF:

0.000417

Gnomad4 SAS exome

AF:

0.000394

Gnomad4 FIN exome

AF:

0.000538

Gnomad4 NFE exome

AF:

0.000290

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.0000682

AC:

AN:

146732

Hom.:

Cov.:

AF XY:

0.0000702

AC XY:

AN XY:

71262

show subpopulations

Gnomad4 AFR

AF:

0.000100

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000600

Gnomad4 OTH

AF:

0.000492

Alfa

AF:

0.000123

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

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

- -

Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.012

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000069

dbscSNV1_RF

Benign

0.0040

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