Variant rs36002196 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004370.6(COL12A1):c.6444A>T(p.Ile2148=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,610,398 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 58 hom. )

Consequence

COL12A1
NM_004370.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.461

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 6-75126367-T-A is Benign according to our data. Variant chr6-75126367-T-A is described in ClinVar as [Benign]. Clinvar id is 475887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.461 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL12A1	NM_004370.6 linkuse as main transcript	c.6444A>T	p.Ile2148=	synonymous_variant	39/66	ENST00000322507.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL12A1	ENST00000322507.13 linkuse as main transcript	c.6444A>T	p.Ile2148=	synonymous_variant	39/66	1	NM_004370.6	P4	Q99715-1
COL12A1	ENST00000345356.10 linkuse as main transcript	c.2952A>T	p.Ile984=	synonymous_variant	24/51	1			Q99715-2
COL12A1	ENST00000483888.6 linkuse as main transcript	c.6444A>T	p.Ile2148=	synonymous_variant	39/65	5		A1
COL12A1	ENST00000416123.6 linkuse as main transcript	c.6444A>T	p.Ile2148=	synonymous_variant	38/63	5			Q99715-4

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2509

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0570

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00444

AC:

1106

AN:

248832

Hom.:

AF XY:

0.00313

AC XY:

422

AN XY:

134982

show subpopulations

Gnomad AFR exome

AF:

0.0617

Gnomad AMR exome

AF:

0.00310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00178

AC:

2591

AN:

1458146

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1072

AN XY:

725430

show subpopulations

Gnomad4 AFR exome

AF:

0.0616

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.00364

GnomAD4 genome

AF:

0.0166

AC:

2528

AN:

152252

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1203

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0573

Gnomad4 AMR

AF:

0.00681

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.0187

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000357

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

6.7

DANN

Benign

0.72

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