rs2734272

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2298T>C(p.Thr766Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,614,154 control chromosomes in the GnomAD database, including 806,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 76076 hom., cov: 32)

Exomes 𝑓: 1.0 ( 730868 hom. )

Consequence

COL1A1
NM_000088.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 0.615

Publications

29 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=-0.54).

BP6

Variant 17-50190862-A-G is Benign according to our data. Variant chr17-50190862-A-G is described in ClinVar as Benign. ClinVar VariationId is 254947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 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.2298T>C	p.Thr766Thr	synonymous	Exon 33 of 51	NP_000079.2	P02452

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL1A1	ENST00000225964.10	TSL:1 MANE Select	c.2298T>C	p.Thr766Thr	synonymous	Exon 33 of 51	ENSP00000225964.6	P02452
COL1A1	ENST00000861334.1		c.2298T>C	p.Thr766Thr	synonymous	Exon 33 of 51	ENSP00000531393.1
COL1A1	ENST00000861339.1		c.2298T>C	p.Thr766Thr	synonymous	Exon 33 of 51	ENSP00000531398.1

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

152096

AN:

152158

Hom.:

76017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.999

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.999

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD2 exomes

AF:

1.00

AC:

251280

AN:

251308

AF XY:

1.00

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1461806

AN:

1461878

Hom.:

730868

Cov.:

AF XY:

1.00

AC XY:

727210

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.999

AC:

33456

AN:

33480

American (AMR)

AF:

1.00

AC:

44718

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26136

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39687

AN:

39700

South Asian (SAS)

AF:

1.00

AC:

86247

AN:

86258

European-Finnish (FIN)

AF:

1.00

AC:

53420

AN:

53420

Middle Eastern (MID)

AF:

1.00

AC:

5768

AN:

5768

European-Non Finnish (NFE)

AF:

1.00

AC:

1111989

AN:

1111998

Other (OTH)

AF:

1.00

AC:

60385

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21672

43344

65016

86688

108360

<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:

1.00

AC:

152214

AN:

152276

Hom.:

76076

Cov.:

AF XY:

1.00

AC XY:

74432

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.999

AC:

41524

AN:

41562

American (AMR)

AF:

0.999

AC:

15275

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5174

AN:

5176

South Asian (SAS)

AF:

1.00

AC:

4820

AN:

4820

European-Finnish (FIN)

AF:

1.00

AC:

10624

AN:

10624

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68012

AN:

68016

Other (OTH)

AF:

1.00

AC:

2109

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

1.00

Hom.:

22048

Bravo

AF:

0.999

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Ehlers-Danlos syndrome, arthrochalasia type (2)

Osteogenesis imperfecta type I (2)

Cardiovascular phenotype (1)

Infantile cortical hyperostosis (1)

Infantile cortical hyperostosis;C0023931:Osteogenesis imperfecta type I;C0029456:Osteoporosis;C0268358:Osteogenesis imperfecta, perinatal lethal;C0268362:Osteogenesis imperfecta type III;C0268363:Osteogenesis imperfecta with normal sclerae, dominant form;C4551623:Ehlers-Danlos syndrome, arthrochalasia type;C5436842:Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 (1)

not provided (1)

Osteogenesis imperfecta (1)

Osteogenesis imperfecta type III (1)

Osteogenesis imperfecta with normal sclerae, dominant form (1)

Osteogenesis imperfecta, perinatal lethal (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

0.61

Mutation Taster

=91/9

disease causing (ClinVar)

(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