dbSNP rs11079898: COL1A1:c.697-30A>G (chr17-50197263-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.697-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,610,468 control chromosomes in the GnomAD database, including 5,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2652 hom., cov: 32)

Exomes 𝑓: 0.031 ( 2954 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.41

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=-0.83).

BP6

Variant 17-50197263-T-C is Benign according to our data. Variant chr17-50197263-T-C is described in ClinVar as [Benign]. Clinvar id is 675133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.697-30A>G	intron_variant	Intron 9 of 50	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.697-30A>G	intron_variant	Intron 9 of 47		XP_011522643.1
COL1A1	XM_005257058.5 link	c.697-30A>G	intron_variant	Intron 9 of 48		XP_005257115.2
COL1A1	XM_005257059.5 link	c.697-30A>G	intron_variant	Intron 9 of 37		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10 link	c.697-30A>G		intron_variant	Intron 9 of 50	1	NM_000088.4	ENSP00000225964.6		P02452
COL1A1	ENST00000495677.1 link	n.424-30A>G		intron_variant	Intron 4 of 7	3

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17480

AN:

151958

Hom.:

2639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0480

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.00944

Gnomad SAS

AF:

0.0567

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0837

GnomAD3 exomes

AF:

0.0481

AC:

12063

AN:

250750

Hom.:

1198

AF XY:

0.0436

AC XY:

5908

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.360

Gnomad AMR exome

AF:

0.0277

Gnomad ASJ exome

AF:

0.0223

Gnomad EAS exome

AF:

0.00615

Gnomad SAS exome

AF:

0.0585

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0351

GnomAD4 exome

AF:

0.0312

AC:

45572

AN:

1458392

Hom.:

2954

Cov.:

AF XY:

0.0314

AC XY:

22763

AN XY:

725658

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.0297

Gnomad4 ASJ exome

AF:

0.0217

Gnomad4 EAS exome

AF:

0.00640

Gnomad4 SAS exome

AF:

0.0595

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0459

GnomAD4 genome

AF:

0.115

AC:

17522

AN:

152076

Hom.:

2652

Cov.:

AF XY:

0.112

AC XY:

8344

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.0478

Gnomad4 ASJ

AF:

0.0276

Gnomad4 EAS

AF:

0.00927

Gnomad4 SAS

AF:

0.0563

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.0212

Gnomad4 OTH

AF:

0.0828

Alfa

AF:

0.0630

Hom.:

214

Bravo

AF:

0.127

Asia WGS

AF:

0.0520

AC:

180

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

-0.83

CADD

Benign

0.49

DANN

Benign

0.33

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