17-50189930-G-C

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.2560-18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,612,158 control chromosomes in the GnomAD database, including 214,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 20984 hom., cov: 32)

Exomes 𝑓: 0.51 ( 193701 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.929

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=-0.77).

BP6

Variant 17-50189930-G-C is Benign according to our data. Variant chr17-50189930-G-C is described in ClinVar as [Benign]. Clinvar id is 254948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50189930-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.2560-18C>G	intron_variant	Intron 36 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.2362-18C>G	intron_variant	Intron 33 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.2560-18C>G	intron_variant	Intron 36 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.1642-18C>G	intron_variant	Intron 23 of 37		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10 link	c.2560-18C>G		intron_variant	Intron 36 of 50	1	NM_000088.4	ENSP00000225964.6		P02452

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79741

AN:

151782

Hom.:

20969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.606

Gnomad AMR

AF:

0.590

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.520

GnomAD3 exomes

AF:

0.522

AC:

129504

AN:

248000

Hom.:

34255

AF XY:

0.517

AC XY:

69401

AN XY:

134152

show subpopulations

Gnomad AFR exome

AF:

0.553

Gnomad AMR exome

AF:

0.640

Gnomad ASJ exome

AF:

0.524

Gnomad EAS exome

AF:

0.521

Gnomad SAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.496

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.513

AC:

749573

AN:

1460256

Hom.:

193701

Cov.:

AF XY:

0.512

AC XY:

371807

AN XY:

726348

show subpopulations

Gnomad4 AFR exome

AF:

0.563

Gnomad4 AMR exome

AF:

0.634

Gnomad4 ASJ exome

AF:

0.520

Gnomad4 EAS exome

AF:

0.556

Gnomad4 SAS exome

AF:

0.518

Gnomad4 FIN exome

AF:

0.451

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.525

AC:

79793

AN:

151902

Hom.:

20984

Cov.:

AF XY:

0.525

AC XY:

38965

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.559

Gnomad4 AMR

AF:

0.591

Gnomad4 ASJ

AF:

0.536

Gnomad4 EAS

AF:

0.524

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.463

Gnomad4 NFE

AF:

0.497

Gnomad4 OTH

AF:

0.519

Alfa

AF:

0.430

Hom.:

2113

Bravo

AF:

0.541

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jun 14, 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

- -

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.77

CADD

Benign

DANN

Benign

0.69

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