7-94403800-C-T

Variant names:

• chr7-94403800-C-T
• rs420257
• NM_000089.4:c.280-756C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000089.4(COL1A2):​c.280-756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,026 control chromosomes in the GnomAD database, including 44,080 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44080 hom., cov: 31)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.280-756C>T		intron_variant	Intron 6 of 51	ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.280-756C>T		intron_variant	Intron 6 of 51	1	NM_000089.4	ENSP00000297268.6

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114718 AN: 151908 Hom.: 44025 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.721

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.755 AC: 114833 AN: 152026 Hom.: 44080 Cov.: 31 AF XY: 0.756 AC XY: 56116 AN XY: 74274

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.723

Alfa AF: 0.701 Hom.: 37682

Bravo AF: 0.766

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.44

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: rs420257; hg19: chr7-94033112;