17-50185660-C-T

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.4249-12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,612,456 control chromosomes in the GnomAD database, including 292,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22816 hom., cov: 29)

Exomes 𝑓: 0.60 ( 269622 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Splicing: ADA: 0.0001039

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0840

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-50185660-C-T is Benign according to our data. Variant chr17-50185660-C-T is described in ClinVar as [Benign]. Clinvar id is 197918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50185660-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.4249-12G>A	intron_variant	Intron 50 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.4051-12G>A	intron_variant	Intron 47 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.3979-12G>A	intron_variant	Intron 48 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.3331-12G>A	intron_variant	Intron 37 of 37		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10 link	c.4249-12G>A		intron_variant	Intron 50 of 50	1	NM_000088.4	ENSP00000225964.6		P02452
COL1A1	ENST00000510710.3 link	n.*184G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

79873

AN:

151354

Hom.:

22803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.694

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.553

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.578

GnomAD3 exomes

AF:

0.590

AC:

146373

AN:

247976

Hom.:

44521

AF XY:

0.592

AC XY:

79534

AN XY:

134314

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.676

Gnomad ASJ exome

AF:

0.691

Gnomad EAS exome

AF:

0.516

Gnomad SAS exome

AF:

0.539

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.628

GnomAD4 exome

AF:

0.604

AC:

882496

AN:

1460984

Hom.:

269622

Cov.:

AF XY:

0.602

AC XY:

437737

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.671

Gnomad4 ASJ exome

AF:

0.695

Gnomad4 EAS exome

AF:

0.549

Gnomad4 SAS exome

AF:

0.538

Gnomad4 FIN exome

AF:

0.625

Gnomad4 NFE exome

AF:

0.616

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.527

AC:

79899

AN:

151472

Hom.:

22816

Cov.:

AF XY:

0.530

AC XY:

39255

AN XY:

73998

show subpopulations

Gnomad4 AFR

AF:

0.283

Gnomad4 AMR

AF:

0.648

Gnomad4 ASJ

AF:

0.694

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.638

Gnomad4 NFE

AF:

0.617

Gnomad4 OTH

AF:

0.578

Alfa

AF:

0.575

Hom.:

5228

Bravo

AF:

0.521

Asia WGS

AF:

0.507

AC:

1766

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Mar 03, 2016

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 04, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 26, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteogenesis imperfecta

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Ehlers-Danlos syndrome, arthrochalasia type

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Infantile cortical hyperostosis

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Osteogenesis imperfecta type I

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.79

CADD

Benign

4.1

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0

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