rs6465412

chr7-94429083-T-Cchr7-94429083-T-G

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.3712-105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 882,434 control chromosomes in the GnomAD database, including 52,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (18182 hom., cov: 28)
  • Exomes 𝑓: 0.27 (34291 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0790

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=-0.88).
• BP6: Variant 7-94429083-T-C is Benign according to our data. Variant chr7-94429083-T-C is described in ClinVar as [Benign]. Clinvar id is 674980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A2	NM_000089.4	c.3712-105T>C		intron_variant		ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A2	ENST00000297268.11	c.3712-105T>C		intron_variant		1	NM_000089.4	P1
COL1A2	ENST00000464916.1	n.760-105T>C		intron_variant, non_coding_transcript_variant		2
COL1A2	ENST00000481570.5	n.4493-105T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 64329 AN: 148958 Hom.: 18133 Cov.: 28

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.266 AC: 194831 AN: 733390 Hom.: 34291 AF XY: 0.262 AC XY: 99411 AN XY: 379944

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.432 AC: 64423 AN: 149044 Hom.: 18182 Cov.: 28 AF XY: 0.426 AC XY: 30957 AN XY: 72614

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.395

Alfa AF: 0.302 Hom.: 6923

Bravo AF: 0.454

Asia WGS AF: 0.435 AC: 1489 AN: 3420

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 19, 2018

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	-0.88
Cadd	Benign	3.0
Dann	Benign	0.47

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: rs6465412; hg19: chr7-94058395;