Variant rs73749974 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 ENST00000322507.13(COL12A1):c.4001-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,604,996 control chromosomes in the GnomAD database, including 265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 141 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 124 hom. )

Consequence

COL12A1
ENST00000322507.13 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002180

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.28

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=-0.92).

BP6

Variant 6-75151297-C-T is Benign according to our data. Variant chr6-75151297-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75151297-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 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.4001-10G>A		splice_polypyrimidine_tract_variant, 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.4001-10G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004370.6	ENSP00000325146	P4	Q99715-1

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3672

AN:

151902

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0226

GnomAD3 exomes

AF:

0.00691

AC:

1696

AN:

245534

Hom.:

AF XY:

0.00525

AC XY:

699

AN XY:

133088

show subpopulations

Gnomad AFR exome

AF:

0.0854

Gnomad AMR exome

AF:

0.00685

Gnomad ASJ exome

AF:

0.00192

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.000573

Gnomad FIN exome

AF:

0.0000472

Gnomad NFE exome

AF:

0.000706

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00292

AC:

4244

AN:

1452976

Hom.:

124

Cov.:

AF XY:

0.00257

AC XY:

1855

AN XY:

721918

show subpopulations

Gnomad4 AFR exome

AF:

0.0852

Gnomad4 AMR exome

AF:

0.00785

Gnomad4 ASJ exome

AF:

0.00259

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000530

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000476

Gnomad4 OTH exome

AF:

0.00628

GnomAD4 genome

AF:

0.0242

AC:

3677

AN:

152020

Hom.:

141

Cov.:

AF XY:

0.0236

AC XY:

1755

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0819

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0286

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 06, 2021	- -

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 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.031

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0060

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