rs35231764

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.588+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,612,788 control chromosomes in the GnomAD database, including 69,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5025 hom., cov: 31)

Exomes 𝑓: 0.29 ( 64516 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0580

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=-0.8).

BP6

Variant 17-50198128-A-G is Benign according to our data. Variant chr17-50198128-A-G is described in ClinVar as [Benign]. Clinvar id is 675050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.588+33T>C	intron_variant	Intron 7 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.588+33T>C	intron_variant	Intron 7 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.588+33T>C	intron_variant	Intron 7 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.588+33T>C	intron_variant	Intron 7 of 37		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10 link	c.588+33T>C		intron_variant	Intron 7 of 50	1	NM_000088.4	ENSP00000225964.6		P02452
COL1A1	ENST00000495677.1 link	n.315+33T>C		intron_variant	Intron 2 of 7	3

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35168

AN:

151910

Hom.:

5022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0587

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.278

AC:

69703

AN:

250554

Hom.:

10439

AF XY:

0.284

AC XY:

38630

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0538

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.207

Gnomad SAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.292

AC:

427009

AN:

1460760

Hom.:

64516

Cov.:

AF XY:

0.293

AC XY:

213023

AN XY:

726736

show subpopulations

Gnomad4 AFR exome

AF:

0.0519

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.285

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.287

GnomAD4 genome

AF:

0.231

AC:

35166

AN:

152028

Hom.:

5025

Cov.:

AF XY:

0.233

AC XY:

17295

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0586

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.286

Gnomad4 FIN

AF:

0.314

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.278

Hom.:

2061

Bravo

AF:

0.219

Asia WGS

AF:

0.230

AC:

799

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 18, 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

-0.80

CADD

Benign

9.1

DANN

Benign

0.78

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