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GeneBe

6-75181096-C-T

Variant summary

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

The NM_004370.6(COL12A1):c.2007G>A(p.Ala669=) 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 1,613,852 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 (★★).

Frequency

Genomes: 𝑓 0.013 ( 40 hom., cov: 32)
Exomes 𝑓: 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: -0.384
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
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-75181096-C-T is Benign according to our data. Variant chr6-75181096-C-T is described in ClinVar as [Benign]. Clinvar id is 259323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75181096-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.384 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1977/151980) while in subpopulation AFR AF= 0.0456 (1887/41422). AF 95% confidence interval is 0.0438. 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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 40 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL12A1NM_004370.6 linkuse as main transcriptc.2007G>A p.Ala669= synonymous_variant 11/66 ENST00000322507.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL12A1ENST00000322507.13 linkuse as main transcriptc.2007G>A p.Ala669= synonymous_variant 11/661 NM_004370.6 P4Q99715-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0130
AC:
1973
AN:
151862
Hom.:
40
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0456
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00453
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:
0.000176
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00350
AC:
872
AN:
249296
Hom.:
23
AF XY:
0.00267
AC XY:
361
AN XY:
135244
show subpopulations
Gnomad AFR exome
AF:
0.0487
Gnomad AMR exome
AF:
0.00244
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.00182
GnomAD4 exome
AF:
0.00139
AC:
2031
AN:
1461872
Hom.:
48
Cov.:
32
AF XY:
0.00116
AC XY:
844
AN XY:
727238
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:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000102
Gnomad4 OTH exome
AF:
0.00351
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0130
AC:
1977
AN:
151980
Hom.:
40
Cov.:
32
AF XY:
0.0127
AC XY:
945
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0456
Gnomad4 AMR
AF:
0.00453
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00497
Hom.:
6
Bravo
AF:
0.0152
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000178

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 testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
1.0
Dann
Benign
0.34

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: rs77790445; hg19: chr6-75890812; API