17-50194694-C-T

Variant summary

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

The NM_000088.4(COL1A1):c.1461+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,558,118 control chromosomes in the GnomAD database, including 361,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (37640 hom., cov: 30)
  • Exomes 𝑓: 0.68 (323749 hom.)
• Consequence: COL1A1 NM_000088.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.19

Genes affected

COL1A1 (HGNC:2197): (collagen type I alpha 1 chain) This gene encodes the pro-alpha1 chains 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 VIIA, Ehlers-Danlos syndrome Classical type, Caffey Disease and idiopathic osteoporosis. Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor. Two 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=-0.84).
• BP6: Variant 17-50194694-C-T is Benign according to our data. Variant chr17-50194694-C-T is described in ClinVar as [Benign]. Clinvar id is 674802.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A1	NM_000088.4	c.1461+27G>A		intron_variant		ENST00000225964.10
COL1A1	XM_005257058.5	c.1461+27G>A		intron_variant
COL1A1	XM_005257059.5	c.957+1620G>A		intron_variant
COL1A1	XM_011524341.2	c.1263+27G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10	c.1461+27G>A		intron_variant		1	NM_000088.4	P1
COL1A1	ENST00000471344.1	n.405+27G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106514 AN: 151674 Hom.: 37599 Cov.: 30

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.712

GnomAD3 exomes AF: 0.685 AC: 114975 AN: 167896 Hom.: 39629 AF XY: 0.678 AC XY: 60560 AN XY: 89278

Gnomad AFR exome AF: 0.756

Gnomad AMR exome AF: 0.768

Gnomad ASJ exome AF: 0.706

Gnomad EAS exome AF: 0.637

Gnomad SAS exome AF: 0.612

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.701

GnomAD4 exome AF: 0.678 AC: 952803 AN: 1406328 Hom.: 323749 Cov.: 38 AF XY: 0.674 AC XY: 468359 AN XY: 694668

Gnomad4 AFR exome AF: 0.757

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.705

Gnomad4 EAS exome AF: 0.641

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.678

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome AF: 0.702 AC: 106610 AN: 151790 Hom.: 37640 Cov.: 30 AF XY: 0.702 AC XY: 52082 AN XY: 74208

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.713

Alfa AF: 0.649 Hom.: 4479

Bravo AF: 0.712

Asia WGS AF: 0.634 AC: 2207 AN: 3478

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 14, 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	-0.84
Cadd	Benign	0.14
Dann	Benign	0.82

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: rs2253369; hg19: chr17-48272055; COSMIC: COSV56806193; COSMIC: COSV56806193;