Variant 6-75134742-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004370.6(COL12A1):c.5508G>A(p.Thr1836=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,605,968 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 149 hom. )

Consequence

COL12A1
NM_004370.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.55

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 6-75134742-C-T is Benign according to our data. Variant chr6-75134742-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75134742-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.55 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00763 (1161/152230) while in subpopulation NFE AF= 0.0119 (810/68012). AF 95% confidence interval is 0.0112. There are 9 homozygotes in gnomad4. There are 503 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL12A1	NM_004370.6 linkuse as main transcript	c.5508G>A	p.Thr1836=	synonymous_variant	32/66	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.5508G>A	p.Thr1836=	synonymous_variant	32/66	1	NM_004370.6	ENSP00000325146	P4	Q99715-1

Frequencies

GnomAD3 genomes

AF:

0.00763

AC:

1160

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00759

AC:

1887

AN:

248772

Hom.:

AF XY:

0.00802

AC XY:

1082

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00349

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00723

Gnomad FIN exome

AF:

0.00228

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00697

GnomAD4 exome

AF:

0.0113

AC:

16453

AN:

1453738

Hom.:

149

Cov.:

AF XY:

0.0112

AC XY:

8106

AN XY:

723270

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.0255

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00692

Gnomad4 FIN exome

AF:

0.00234

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00763

AC:

1161

AN:

152230

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

503

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00222

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.0279

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00766

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	COL12A1: BP4, BP7, BS1, BS2 -

Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 11, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.36

DANN

Benign

0.38

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