chr7-94405377-C-T

Variant names:

• chr7-94405377-C-T
• rs28417792
• NM_000089.4:c.486+125C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000089.4(COL1A2):​c.486+125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 932,014 control chromosomes in the GnomAD database, including 6,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2973 hom., cov: 32)
  • Exomes 𝑓: 0.041 (3513 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.799

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-94405377-C-T is Benign according to our data. Variant chr7-94405377-C-T is described in ClinVar as [Benign]. Clinvar id is 678457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.486+125C>T		intron_variant	Intron 10 of 51	ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.486+125C>T		intron_variant	Intron 10 of 51	1	NM_000089.4	ENSP00000297268.6

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18974 AN: 151576 Hom.: 2962 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0407 AC: 31764 AN: 780320 Hom.: 3513 AF XY: 0.0397 AC XY: 16038 AN XY: 404342

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.0655

Gnomad4 ASJ exome AF: 0.0155

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.0525

Gnomad4 FIN exome AF: 0.0314

Gnomad4 NFE exome AF: 0.00963

Gnomad4 OTH exome AF: 0.0599

GnomAD4 genome AF: 0.125 AC: 19037 AN: 151694 Hom.: 2973 Cov.: 32 AF XY: 0.127 AC XY: 9398 AN XY: 74110

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0321

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0812 Hom.: 184

Bravo AF: 0.140

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 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	-0.81
CADD	Benign	4.5
DANN	Benign	0.48

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: rs28417792; hg19: chr7-94034689; COSMIC: COSV51958388;