7-94406121-C-T

Position:

• chr7-94406121-C-T

Variant summary

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

The ENST00000297268.11(COL1A2):​c.541-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 926,898 control chromosomes in the GnomAD database, including 4,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (618 hom., cov: 32)
  • Exomes 𝑓: 0.094 (3960 hom.)
• Consequence: COL1A2 ENST00000297268.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.224

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 7-94406121-C-T is Benign according to our data. Variant chr7-94406121-C-T is described in ClinVar as [Benign]. Clinvar id is 1297451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.541-129C>T		intron_variant		ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.541-129C>T		intron_variant		1	NM_000089.4	ENSP00000297268	P1

Frequencies

GnomAD3 genomes AF: 0.0815 AC: 12397 AN: 152120 Hom.: 617 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0980

GnomAD4 exome AF: 0.0938 AC: 72670 AN: 774660 Hom.: 3960 AF XY: 0.0911 AC XY: 36995 AN XY: 406014

Gnomad4 AFR exome AF: 0.0376

Gnomad4 AMR exome AF: 0.0710

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.0000302

Gnomad4 SAS exome AF: 0.0267

Gnomad4 FIN exome AF: 0.0800

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.0962

GnomAD4 genome AF: 0.0814 AC: 12393 AN: 152238 Hom.: 618 Cov.: 32 AF XY: 0.0778 AC XY: 5790 AN XY: 74430

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.0875

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.0989 Hom.: 165

Bravo AF: 0.0823

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17073; hg19: chr7-94035433;