17-50194694-C-T

Variant names:

Variant summary

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

The NM_000088.4(COL1A1):c.1461+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,558,118 control chromosomes in the GnomAD database, including 361,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37640 hom., cov: 30)

Exomes 𝑓: 0.68 ( 323749 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.19

Publications

16 publications found

Variant links:

Genes affected

COL1A1 (HGNC:2197): (collagen type I alpha 1 chain) This gene encodes the pro-alpha1 chains of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIA, Ehlers-Danlos syndrome Classical type, Caffey Disease and idiopathic osteoporosis. Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor. Two transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]

COL1A1 Gene-Disease associations (from GenCC):

Caffey disease
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
COL1A1-related Ehlers-Danlos syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, Ambry Genetics
Ehlers-Danlos syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Ehlers-Danlos syndrome, arthrochalasia type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
osteogenesis imperfecta
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
osteogenesis imperfecta type 1
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
osteogenesis imperfecta type 2
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
osteogenesis imperfecta type 3
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
osteogenesis imperfecta type 4
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet
Ehlers-Danlos syndrome, classic type, 1
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
Ehlers-Danlos syndrome, classic type
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ehlers-Danlos/osteogenesis imperfecta syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
high bone mass osteogenesis imperfecta
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL1A1 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=-0.84).

BP6

Variant 17-50194694-C-T is Benign according to our data. Variant chr17-50194694-C-T is described in ClinVar as Benign. ClinVar VariationId is 674802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000088.4. 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
	COL1A1	NM_000088.4	MANE Select	c.1461+27G>A		intron	N/A	NP_000079.2	P02452

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL1A1	ENST00000225964.10	TSL:1 MANE Select	c.1461+27G>A	intron	N/A	ENSP00000225964.6	P02452
COL1A1	ENST00000861334.1		c.1461+27G>A	intron	N/A	ENSP00000531393.1
COL1A1	ENST00000861339.1		c.1461+27G>A	intron	N/A	ENSP00000531398.1

Frequencies

GnomAD3 genomes

AF:

0.702

AC:

106514

AN:

151674

Hom.:

37599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.697

Gnomad AMR

AF:

0.746

Gnomad ASJ

AF:

0.699

Gnomad EAS

AF:

0.627

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.688

Gnomad MID

AF:

0.675

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.712

GnomAD2 exomes

AF:

0.685

AC:

114975

AN:

167896

AF XY:

0.678

show subpopulations

Gnomad AFR exome

AF:

0.756

Gnomad AMR exome

AF:

0.768

Gnomad ASJ exome

AF:

0.706

Gnomad EAS exome

AF:

0.637

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.675

Gnomad OTH exome

AF:

0.701

GnomAD4 exome

AF:

0.678

AC:

952803

AN:

1406328

Hom.:

323749

Cov.:

AF XY:

0.674

AC XY:

468359

AN XY:

694668

show subpopulations

African (AFR)

AF:

0.757

AC:

24126

AN:

31850

American (AMR)

AF:

0.763

AC:

27914

AN:

36574

Ashkenazi Jewish (ASJ)

AF:

0.705

AC:

17823

AN:

25282

East Asian (EAS)

AF:

0.641

AC:

23192

AN:

36186

South Asian (SAS)

AF:

0.611

AC:

49105

AN:

80350

European-Finnish (FIN)

AF:

0.676

AC:

33510

AN:

49558

Middle Eastern (MID)

AF:

0.681

AC:

3884

AN:

5702

European-Non Finnish (NFE)

AF:

0.678

AC:

733631

AN:

1082508

Other (OTH)

AF:

0.679

AC:

39618

AN:

58318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

18291

36582

54873

73164

91455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19118

38236

57354

76472

95590

<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:

0.702

AC:

106610

AN:

151790

Hom.:

37640

Cov.:

AF XY:

0.702

AC XY:

52082

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.753

AC:

31161

AN:

41376

American (AMR)

AF:

0.746

AC:

11395

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

2424

AN:

3470

East Asian (EAS)

AF:

0.627

AC:

3213

AN:

5122

South Asian (SAS)

AF:

0.636

AC:

3063

AN:

4818

European-Finnish (FIN)

AF:

0.688

AC:

7255

AN:

10546

Middle Eastern (MID)

AF:

0.695

AC:

203

AN:

292

European-Non Finnish (NFE)

AF:

0.674

AC:

45761

AN:

67872

Other (OTH)

AF:

0.713

AC:

1502

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1506

3012

4518

6024

7530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.649

Hom.:

4479

Bravo

AF:

0.712

Asia WGS

AF:

0.634

AC:

2207

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.14

(source)

DANN

Benign

0.82

PhyloP100

-2.2

Mutation Taster

=52/48

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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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