rs4729131

chr7-94399115-G-Achr7-94399115-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0210

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
COL1A2	NM_000089.4	c.132+31G>A		intron_variant		ENST00000297268.11

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25424 AN: 151908 Hom.: 2387 Cov.: 32

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

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.: 28 AF XY: 0.181 AC XY: 130559 AN XY: 720626

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.: 32 AF XY: 0.173 AC XY: 12884 AN XY: 74294

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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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

Other links and lift over

dbSNP: rs4729131; hg19: chr7-94028427; COSMIC: COSV51958701; COSMIC: COSV51958701;