chr17-50186542-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000088.4(COL1A1):c.3815-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,676 control chromosomes in the GnomAD database, including 23,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3244 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20724 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.00700

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 17-50186542-A-G is Benign according to our data. Variant chr17-50186542-A-G is described in ClinVar as [Benign]. Clinvar id is 674809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.3815-35T>C	intron_variant	Intron 48 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.3617-35T>C	intron_variant	Intron 45 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.3545-35T>C	intron_variant	Intron 46 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.2897-35T>C	intron_variant	Intron 35 of 37		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10 link	c.3815-35T>C		intron_variant	Intron 48 of 50	1	NM_000088.4	ENSP00000225964.6		P02452
COL1A1	ENST00000510710.3 link	n.484-35T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

28992

AN:

151902

Hom.:

3241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.179

AC:

44868

AN:

251100

Hom.:

4986

AF XY:

0.182

AC XY:

24771

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.0701

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.364

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.159

AC:

232358

AN:

1461656

Hom.:

20724

Cov.:

AF XY:

0.162

AC XY:

118140

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.297

Gnomad4 AMR exome

AF:

0.0735

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.143

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.191

AC:

29029

AN:

152020

Hom.:

3244

Cov.:

AF XY:

0.193

AC XY:

14313

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.358

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.145

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.148

Hom.:

1868

Bravo

AF:

0.191

Asia WGS

AF:

0.309

AC:

1073

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Osteogenesis imperfecta type III

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteogenesis imperfecta with normal sclerae, dominant form

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, arthrochalasia type

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteogenesis imperfecta, perinatal lethal

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteogenesis imperfecta type I

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: 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

-0.86

CADD

Benign

1.3

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over