chr21-46000809-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001848.3(COL6A1):c.1822+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,611,126 control chromosomes in the GnomAD database, including 75,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7972 hom., cov: 36)

Exomes 𝑓: 0.30 ( 67420 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.554

Publications

10 publications found

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]

COL6A1 Gene-Disease associations (from GenCC):

Bethlem myopathy 1A
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
collagen 6-related myopathy
Inheritance: SD, AD, AR Classification: DEFINITIVE Submitted by: ClinGen
Ullrich congenital muscular dystrophy 1A
Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Bethlem myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ullrich congenital muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL6A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-46000809-G-C is Benign according to our data. Variant chr21-46000809-G-C is described in ClinVar as Benign. ClinVar VariationId is 93831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001848.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A1	NM_001848.3	MANE Select	c.1822+42G>C		intron	N/A	NP_001839.2	P12109

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL6A1	ENST00000361866.8	TSL:1 MANE Select	c.1822+42G>C	intron	N/A	ENSP00000355180.3	P12109
COL6A1	ENST00000866134.1		c.565-1718G>C	intron	N/A	ENSP00000536193.1
COL6A1	ENST00000466285.1	TSL:3	n.381G>C	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48266

AN:

152094

Hom.:

7964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.298

GnomAD2 exomes

AF:

0.281

AC:

70527

AN:

250916

AF XY:

0.276

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.300

AC:

438392

AN:

1458914

Hom.:

67420

Cov.:

AF XY:

0.297

AC XY:

215782

AN XY:

725956

show subpopulations

African (AFR)

AF:

0.393

AC:

13141

AN:

33414

American (AMR)

AF:

0.297

AC:

13301

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

5875

AN:

26114

East Asian (EAS)

AF:

0.189

AC:

7498

AN:

39678

South Asian (SAS)

AF:

0.232

AC:

20016

AN:

86216

European-Finnish (FIN)

AF:

0.272

AC:

14428

AN:

53044

Middle Eastern (MID)

AF:

0.242

AC:

1396

AN:

5758

European-Non Finnish (NFE)

AF:

0.312

AC:

345853

AN:

1109694

Other (OTH)

AF:

0.280

AC:

16884

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16997

33994

50992

67989

84986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11284

22568

33852

45136

56420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.317

AC:

48302

AN:

152212

Hom.:

7972

Cov.:

AF XY:

0.317

AC XY:

23550

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.392

AC:

16297

AN:

41552

American (AMR)

AF:

0.323

AC:

4940

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

778

AN:

3470

East Asian (EAS)

AF:

0.161

AC:

834

AN:

5180

South Asian (SAS)

AF:

0.220

AC:

1065

AN:

4830

European-Finnish (FIN)

AF:

0.276

AC:

2929

AN:

10600

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.303

AC:

20612

AN:

67964

Other (OTH)

AF:

0.294

AC:

621

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1754

3509

5263

7018

8772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.213

Hom.:

650

Bravo

AF:

0.325

Asia WGS

AF:

0.177

AC:

620

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.35

(source)

DANN

Benign

0.60

PhyloP100

0.55

PromoterAI

-0.091

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over