rs769487412
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1
The NM_001848.3(COL6A1):c.1003-15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,612,878 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.000092 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00024 ( 1 hom. )
Consequence
COL6A1
NM_001848.3 intron
NM_001848.3 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.144
Genes affected
COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
?
Variant 21-45990754-GT-G is Benign according to our data. Variant chr21-45990754-GT-G is described in ClinVar as [Likely_benign]. Clinvar id is 258283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00024 (351/1460756) while in subpopulation SAS AF= 0.00395 (341/86226). AF 95% confidence interval is 0.00361. There are 1 homozygotes in gnomad4_exome. There are 264 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.1003-15del | intron_variant | ENST00000361866.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A1 | ENST00000361866.8 | c.1003-15del | intron_variant | 1 | NM_001848.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152122Hom.: 1 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
14
AN:
152122
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000427 AC: 107AN: 250612Hom.: 0 AF XY: 0.000611 AC XY: 83AN XY: 135772
GnomAD3 exomes
AF:
AC:
107
AN:
250612
Hom.:
AF XY:
AC XY:
83
AN XY:
135772
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000240 AC: 351AN: 1460756Hom.: 1 Cov.: 33 AF XY: 0.000363 AC XY: 264AN XY: 726720
GnomAD4 exome
AF:
AC:
351
AN:
1460756
Hom.:
Cov.:
33
AF XY:
AC XY:
264
AN XY:
726720
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152122Hom.: 1 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74310
GnomAD4 genome
?
AF:
AC:
14
AN:
152122
Hom.:
Cov.:
33
AF XY:
AC XY:
10
AN XY:
74310
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
4
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 05, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BranchPoint Hunter
?
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at