dbSNP rs2141279: COL1A1:c.1002+52A>G (chr17-50196103-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000088.4(COL1A1):c.1002+52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 1,612,242 control chromosomes in the GnomAD database, including 574,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 57149 hom., cov: 32)

Exomes 𝑓: 0.84 ( 517811 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.472

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=-0.85).

BP6

Variant 17-50196103-T-C is Benign according to our data. Variant chr17-50196103-T-C is described in ClinVar as [Benign]. Clinvar id is 674801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.1002+52A>G	intron_variant	Intron 15 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.957+211A>G	intron_variant	Intron 14 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.1002+52A>G	intron_variant	Intron 15 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.957+211A>G	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.1002+52A>G		intron_variant	Intron 15 of 50	1	NM_000088.4	ENSP00000225964.6		P02452
COL1A1	ENST00000485870.1 link	n.379A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.864

AC:

131442

AN:

152070

Hom.:

57106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.942

Gnomad AMI

AF:

0.878

Gnomad AMR

AF:

0.833

Gnomad ASJ

AF:

0.899

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.801

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.847

Gnomad OTH

AF:

0.860

GnomAD4 exome

AF:

0.841

AC:

1228225

AN:

1460054

Hom.:

517811

Cov.:

AF XY:

0.841

AC XY:

610763

AN XY:

726400

show subpopulations

Gnomad4 AFR exome

AF:

0.949

Gnomad4 AMR exome

AF:

0.805

Gnomad4 ASJ exome

AF:

0.919

Gnomad4 EAS exome

AF:

0.689

Gnomad4 SAS exome

AF:

0.818

Gnomad4 FIN exome

AF:

0.813

Gnomad4 NFE exome

AF:

0.846

Gnomad4 OTH exome

AF:

0.844

GnomAD4 genome

AF:

0.864

AC:

131542

AN:

152188

Hom.:

57149

Cov.:

AF XY:

0.861

AC XY:

64012

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.942

Gnomad4 AMR

AF:

0.833

Gnomad4 ASJ

AF:

0.899

Gnomad4 EAS

AF:

0.709

Gnomad4 SAS

AF:

0.800

Gnomad4 FIN

AF:

0.812

Gnomad4 NFE

AF:

0.847

Gnomad4 OTH

AF:

0.856

Alfa

AF:

0.849

Hom.:

6850

Bravo

AF:

0.871

Asia WGS

AF:

0.733

AC:

2547

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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