rs41317361

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.1300-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,613,534 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 152 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 151 hom. )

Consequence

COL1A1
NM_000088.4 splice_region, intron

Scores

Splicing: ADA: 0.00002383

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.517

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=-0.81).

BP6

Variant 17-50195108-G-A is Benign according to our data. Variant chr17-50195108-G-A is described in ClinVar as [Benign]. Clinvar id is 195451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50195108-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.1300-8C>T	splice_region_variant, intron_variant	Intron 19 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.1102-8C>T	splice_region_variant, intron_variant	Intron 16 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.1300-8C>T	splice_region_variant, intron_variant	Intron 19 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.957+1206C>T	intron_variant	Intron 14 of 37		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10 link	c.1300-8C>T		splice_region_variant, intron_variant	Intron 19 of 50	1	NM_000088.4	ENSP00000225964.6		P02452
COL1A1	ENST00000471344.1 link	n.244-8C>T		splice_region_variant, intron_variant	Intron 3 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3493

AN:

152042

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0779

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000633

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00715

AC:

1793

AN:

250786

Hom.:

AF XY:

0.00529

AC XY:

717

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.0798

Gnomad AMR exome

AF:

0.00440

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.0000935

Gnomad NFE exome

AF:

0.000626

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00317

AC:

4629

AN:

1461374

Hom.:

151

Cov.:

AF XY:

0.00295

AC XY:

2145

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.0865

Gnomad4 AMR exome

AF:

0.00476

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.00228

Gnomad4 FIN exome

AF:

0.0000752

Gnomad4 NFE exome

AF:

0.000339

Gnomad4 OTH exome

AF:

0.00762

GnomAD4 genome

AF:

0.0231

AC:

3513

AN:

152160

Hom.:

152

Cov.:

AF XY:

0.0222

AC XY:

1650

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0782

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000633

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00303

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 05, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 04, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 31, 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. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteogenesis imperfecta

Benign:2

Mar 19, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome

Benign:1

Oct 19, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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

Jan 30, 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

-0.81

CADD

Benign

1.1

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

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