chr17-50187848-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000088.4(COL1A1):c.3369+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,552,920 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 30 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.878

Publications

1 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen
combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
Ehlers-Danlos syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Ehlers-Danlos syndrome, arthrochalasia type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
osteogenesis imperfecta type 1
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
osteogenesis imperfecta type 2
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
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: G2P, Orphanet, ClinGen
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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-50187848-G-A is Benign according to our data. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-50187848-G-A is described in CliVar as Likely_benign. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000788 (120/152302) while in subpopulation EAS AF = 0.0226 (117/5178). AF 95% confidence interval is 0.0193. There are 5 homozygotes in GnomAd4. There are 74 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 120 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.3369+28C>T	intron_variant	Intron 45 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.3171+28C>T	intron_variant	Intron 42 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.3099+28C>T	intron_variant	Intron 43 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.2451+28C>T	intron_variant	Intron 32 of 37		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL1A1	ENST00000225964.10 link	c.3369+28C>T	intron_variant	Intron 45 of 50	1	NM_000088.4	ENSP00000225964.6	P02452
COL1A1	ENST00000486572.1 link	n.595C>T	non_coding_transcript_exon_variant	Exon 2 of 2	3
COL1A1	ENST00000511732.1 link	n.*44C>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00154

AC:

333

AN:

216436

AF XY:

0.00141

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000821

Gnomad OTH exome

AF:

0.000384

GnomAD4 exome

AF:

0.00107

AC:

1497

AN:

1400618

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

700

AN XY:

693908

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32072

American (AMR)

AF:

0.00

AC:

AN:

40908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22982

East Asian (EAS)

AF:

0.0361

AC:

1420

AN:

39304

South Asian (SAS)

AF:

0.0000634

AC:

AN:

78810

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

0.0000373

AC:

AN:

1072272

Other (OTH)

AF:

0.000535

AC:

AN:

57892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

103

206

310

413

516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000788

AC:

120

AN:

152302

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41570

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0226

AC:

117

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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

<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:

0.000271

Hom.:

Bravo

AF:

0.000548

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 21, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.8

(source)

DANN

Benign

0.65

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism

(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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over