rs34767467

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.1551A>Gā€‹(p.Thr517Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,614,230 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.013 ( 40 hom., cov: 32)
Exomes š‘“: 0.0014 ( 48 hom. )

Consequence

COL12A1
NM_004370.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.34
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]

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=-0.94).
BP6
Variant 6-75183390-T-C is Benign according to our data. Variant chr6-75183390-T-C is described in ClinVar as [Benign]. Clinvar id is 259319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75183390-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.34 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1983/152366) while in subpopulation AFR AF= 0.0456 (1895/41584). AF 95% confidence interval is 0.0439. There are 40 homozygotes in gnomad4. There are 945 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 40 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL12A1NM_004370.6 linkuse as main transcriptc.1551A>G p.Thr517Thr synonymous_variant 10/66 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.1551A>G p.Thr517Thr synonymous_variant 10/661 NM_004370.6 ENSP00000325146.8 Q99715-1

Frequencies

GnomAD3 genomes
AF:
0.0130
AC:
1979
AN:
152248
Hom.:
40
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0456
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00451
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00349
AC:
870
AN:
249414
Hom.:
23
AF XY:
0.00267
AC XY:
361
AN XY:
135312
show subpopulations
Gnomad AFR exome
AF:
0.0487
Gnomad AMR exome
AF:
0.00243
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00182
GnomAD4 exome
AF:
0.00138
AC:
2024
AN:
1461864
Hom.:
48
Cov.:
31
AF XY:
0.00115
AC XY:
839
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0464
Gnomad4 AMR exome
AF:
0.00264
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000971
Gnomad4 OTH exome
AF:
0.00351
GnomAD4 genome
AF:
0.0130
AC:
1983
AN:
152366
Hom.:
40
Cov.:
32
AF XY:
0.0127
AC XY:
945
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.0456
Gnomad4 AMR
AF:
0.00451
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00721
Hom.:
11
Bravo
AF:
0.0152
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxAug 15, 2019- -
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.34
DANN
Benign
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs34767467; hg19: chr6-75893106; API