Variant rs4729131 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_000089.4(COL1A2):c.132+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,598,662 control chromosomes in the GnomAD database, including 26,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2384 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24022 hom. )

Consequence

COL1A2
NM_000089.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0210

Variant links:

Genes affected

COL1A2 (HGNC:2198): (collagen type I alpha 2 chain) This gene encodes the pro-alpha2 chain 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 VIIB, recessive Ehlers-Danlos syndrome Classical type, idiopathic osteoporosis, and atypical Marfan syndrome. Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity. Three transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]

COL1A2 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 7-94399115-G-A is Benign according to our data. Variant chr7-94399115-G-A is described in ClinVar as [Benign]. Clinvar id is 1271287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A2	NM_000089.4 linkuse as main transcript	c.132+31G>A		intron_variant		ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11 linkuse as main transcript	c.132+31G>A		intron_variant		1	NM_000089.4	ENSP00000297268	P1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25424

AN:

151908

Hom.:

2387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.192

AC:

48247

AN:

251194

Hom.:

5006

AF XY:

0.198

AC XY:

26825

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.277

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.178

AC:

256870

AN:

1446636

Hom.:

24022

Cov.:

AF XY:

0.181

AC XY:

130559

AN XY:

720626

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.264

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.167

AC:

25411

AN:

152026

Hom.:

2384

Cov.:

AF XY:

0.173

AC XY:

12884

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.265

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.172

Hom.:

4018

Bravo

AF:

0.152

Asia WGS

AF:

0.218

AC:

758

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.8

DANN

Benign

0.72

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