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rs148909683

chr21-45989808-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001848.3(COL6A1):c.930+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00486 in 1,612,636 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0050 ( 35 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.05
Variant links:
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 -20 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=-0.91).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-45989808-T-C is Benign according to our data. Variant chr21-45989808-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00396 (603/152226) while in subpopulation NFE AF= 0.00529 (360/67992). AF 95% confidence interval is 0.00484. There are 4 homozygotes in gnomad4. There are 306 alleles in male gnomad4 subpopulation. Median coverage is 33. 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 4 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL6A1NM_001848.3 linkuse as main transcriptc.930+30T>C intron_variant ENST00000361866.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL6A1ENST00000361866.8 linkuse as main transcriptc.930+30T>C intron_variant 1 NM_001848.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00396
AC:
603
AN:
152108
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000942
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00260
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0168
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00529
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00457
AC:
1142
AN:
250076
Hom.:
3
AF XY:
0.00462
AC XY:
626
AN XY:
135624
show subpopulations
Gnomad AFR exome
AF:
0.000806
Gnomad AMR exome
AF:
0.000521
Gnomad ASJ exome
AF:
0.00120
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.0174
Gnomad NFE exome
AF:
0.00614
Gnomad OTH exome
AF:
0.00426
GnomAD4 exome
AF:
0.00496
AC:
7239
AN:
1460410
Hom.:
35
Cov.:
37
AF XY:
0.00478
AC XY:
3471
AN XY:
726500
show subpopulations
Gnomad4 AFR exome
AF:
0.000627
Gnomad4 AMR exome
AF:
0.000693
Gnomad4 ASJ exome
AF:
0.00149
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.0173
Gnomad4 NFE exome
AF:
0.00534
Gnomad4 OTH exome
AF:
0.00485
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00396
AC:
603
AN:
152226
Hom.:
4
Cov.:
33
AF XY:
0.00411
AC XY:
306
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000939
Gnomad4 AMR
AF:
0.000653
Gnomad4 ASJ
AF:
0.00260
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0168
Gnomad4 NFE
AF:
0.00529
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00491
Hom.:
0
Bravo
AF:
0.00262
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: 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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
Cadd
Benign
0.78
Dann
Benign
0.42

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: rs148909683; hg19: chr21-47409722; API