rs2586488

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000088.4(COL1A1):c.3261+31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,612,540 control chromosomes in the GnomAD database, including 376,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33444 hom., cov: 33)

Exomes 𝑓: 0.68 ( 343528 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.761

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=-0.84).

BP6

Variant 17-50188065-A-G is Benign according to our data. Variant chr17-50188065-A-G is described in ClinVar as [Benign]. Clinvar id is 674808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.3261+31T>C	intron_variant	Intron 44 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.3063+31T>C	intron_variant	Intron 41 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.2991+31T>C	intron_variant	Intron 42 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.2343+31T>C	intron_variant	Intron 31 of 37		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL1A1	ENST00000225964.10 link	c.3261+31T>C	intron_variant	Intron 44 of 50	1	NM_000088.4	ENSP00000225964.6	P02452
COL1A1	ENST00000511732.1 link	n.616T>C	non_coding_transcript_exon_variant	Exon 2 of 2	2
COL1A1	ENST00000486572.1 link	n.459+31T>C	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

100302

AN:

152006

Hom.:

33421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.581

Gnomad AMI

AF:

0.836

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.748

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.691

Gnomad OTH

AF:

0.684

GnomAD3 exomes

AF:

0.670

AC:

166345

AN:

248426

Hom.:

56155

AF XY:

0.668

AC XY:

89834

AN XY:

134404

show subpopulations

Gnomad AFR exome

AF:

0.575

Gnomad AMR exome

AF:

0.724

Gnomad ASJ exome

AF:

0.744

Gnomad EAS exome

AF:

0.527

Gnomad SAS exome

AF:

0.604

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.693

Gnomad OTH exome

AF:

0.707

GnomAD4 exome

AF:

0.684

AC:

999503

AN:

1460416

Hom.:

343528

Cov.:

AF XY:

0.681

AC XY:

494916

AN XY:

726378

show subpopulations

Gnomad4 AFR exome

AF:

0.581

Gnomad4 AMR exome

AF:

0.722

Gnomad4 ASJ exome

AF:

0.745

Gnomad4 EAS exome

AF:

0.556

Gnomad4 SAS exome

AF:

0.604

Gnomad4 FIN exome

AF:

0.701

Gnomad4 NFE exome

AF:

0.695

Gnomad4 OTH exome

AF:

0.681

GnomAD4 genome

AF:

0.660

AC:

100370

AN:

152124

Hom.:

33444

Cov.:

AF XY:

0.660

AC XY:

49082

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.581

Gnomad4 AMR

AF:

0.717

Gnomad4 ASJ

AF:

0.748

Gnomad4 EAS

AF:

0.531

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.716

Gnomad4 NFE

AF:

0.691

Gnomad4 OTH

AF:

0.683

Alfa

AF:

0.690

Hom.:

59444

Bravo

AF:

0.661

Asia WGS

AF:

0.556

AC:

1935

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 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. -

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

-0.84

CADD

Benign

1.5

DANN

Benign

0.42

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