rs41316671

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.1875+41G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,614,036 control chromosomes in the GnomAD database, including 530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 75 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 455 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0690

Publications

3 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, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), 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), Orphanet, Genomics England PanelApp
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

new If you want to explore the variant's impact on the transcript NM_000088.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.8).

BP6

Variant 17-50192756-C-G is Benign according to our data. Variant chr17-50192756-C-G is described in ClinVar as Benign. ClinVar VariationId is 679029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 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.1875+41G>C		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.1875+41G>C	intron	N/A	ENSP00000225964.6	P02452
COL1A1	ENST00000861334.1		c.1875+41G>C	intron	N/A	ENSP00000531393.1
COL1A1	ENST00000861339.1		c.1875+41G>C	intron	N/A	ENSP00000531398.1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2357

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0276

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.0340

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.0217

AC:

5452

AN:

251266

AF XY:

0.0200

show subpopulations

Gnomad AFR exome

AF:

0.0282

Gnomad AMR exome

AF:

0.0455

Gnomad ASJ exome

AF:

0.0155

Gnomad EAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.00782

AC:

11426

AN:

1461776

Hom.:

455

Cov.:

AF XY:

0.00812

AC XY:

5906

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.0266

AC:

892

AN:

33476

American (AMR)

AF:

0.0456

AC:

2037

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0151

AC:

394

AN:

26136

East Asian (EAS)

AF:

0.113

AC:

4493

AN:

39700

South Asian (SAS)

AF:

0.0289

AC:

2489

AN:

86254

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000227

AC:

252

AN:

1111942

Other (OTH)

AF:

0.0138

AC:

835

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

832

1665

2497

3330

4162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

0.0156

AC:

2373

AN:

152260

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1220

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0259

AC:

1077

AN:

41534

American (AMR)

AF:

0.0276

AC:

422

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3472

East Asian (EAS)

AF:

0.116

AC:

600

AN:

5172

South Asian (SAS)

AF:

0.0336

AC:

162

AN:

4816

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68028

Other (OTH)

AF:

0.0137

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

105

210

316

421

526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00893

Hom.:

Bravo

AF:

0.0190

Asia WGS

AF:

0.0820

AC:

283

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

-0.80

CADD

Benign

5.5

(source)

DANN

Benign

0.50

PhyloP100

0.069

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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