Variant chr17-50185414-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000088.4(COL1A1):c.*88T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,493,578 control chromosomes in the GnomAD database, including 60,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7607 hom., cov: 28)

Exomes 𝑓: 0.27 ( 53077 hom. )

Consequence

COL1A1
NM_000088.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.707

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=-0.86).

BP6

Variant 17-50185414-A-G is Benign according to our data. Variant chr17-50185414-A-G is described in ClinVar as [Benign]. Clinvar id is 324093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
COL1A1	NM_000088.4 linkuse as main transcript	c.*88T>C	3_prime_UTR_variant	51/51	ENST00000225964.10
COL1A1	XM_005257058.5 linkuse as main transcript	c.*88T>C	3_prime_UTR_variant	49/49
COL1A1	XM_005257059.5 linkuse as main transcript	c.*88T>C	3_prime_UTR_variant	38/38
COL1A1	XM_011524341.2 linkuse as main transcript	c.*88T>C	3_prime_UTR_variant	48/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10 linkuse as main transcript	c.*88T>C		3_prime_UTR_variant	51/51	1	NM_000088.4	P1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

46657

AN:

150490

Hom.:

7588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.298

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.295

GnomAD4 exome

AF:

0.275

AC:

368744

AN:

1342968

Hom.:

53077

Cov.:

AF XY:

0.280

AC XY:

187820

AN XY:

670756

show subpopulations

Gnomad4 AFR exome

AF:

0.389

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.442

Gnomad4 SAS exome

AF:

0.401

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.310

AC:

46706

AN:

150610

Hom.:

7607

Cov.:

AF XY:

0.309

AC XY:

22703

AN XY:

73462

show subpopulations

Gnomad4 AFR

AF:

0.397

Gnomad4 AMR

AF:

0.267

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.390

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.261

Hom.:

5369

Bravo

AF:

0.317

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Osteogenesis imperfecta

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Ehlers-Danlos syndrome, arthrochalasia type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Infantile cortical hyperostosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.2

DANN

Benign

0.59

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