rs202239067

Variant summary

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

The NM_004370.6(COL12A1):ā€‹c.8565A>Gā€‹(p.Pro2855Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,613,856 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00012 ( 0 hom., cov: 33)
Exomes š‘“: 0.00028 ( 3 hom. )

Consequence

COL12A1
NM_004370.6 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.21
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 6-75097265-T-C is Benign according to our data. Variant chr6-75097265-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 475903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75097265-T-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.21 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000118 (18/152310) while in subpopulation SAS AF= 0.00332 (16/4824). AF 95% confidence interval is 0.00208. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL12A1NM_004370.6 linkuse as main transcriptc.8565A>G p.Pro2855Pro synonymous_variant 59/66 ENST00000322507.13 NP_004361.3 Q99715-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL12A1ENST00000322507.13 linkuse as main transcriptc.8565A>G p.Pro2855Pro synonymous_variant 59/661 NM_004370.6 ENSP00000325146.8 Q99715-1

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00331
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000590
AC:
147
AN:
249324
Hom.:
0
AF XY:
0.000739
AC XY:
100
AN XY:
135282
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00478
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000281
AC:
410
AN:
1461546
Hom.:
3
Cov.:
30
AF XY:
0.000396
AC XY:
288
AN XY:
727100
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00448
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.000175
AC XY:
13
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00332
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000905
Hom.:
0
Bravo
AF:
0.0000302
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

COL12A1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 13, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024COL12A1: BP4, BP7 -
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 21, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
2.5
DANN
Benign
0.67

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.

Other links and lift over

dbSNP: rs202239067; hg19: chr6-75806981; COSMIC: COSV100485593; API