17-50199610-G-C

Position:

• chr17-50199610-G-C

Variant summary

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

The NM_000088.4(COL1A1):​c.299-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 1,613,412 control chromosomes in the GnomAD database, including 347,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (25709 hom., cov: 32)
  • Exomes 𝑓: 0.66 (322222 hom.)
• Consequence: COL1A1 NM_000088.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.238

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-50199610-G-C is Benign according to our data. Variant chr17-50199610-G-C is described in ClinVar as [Benign]. Clinvar id is 254949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50199610-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A1	NM_000088.4	c.299-20C>G		intron_variant		ENST00000225964.10	NP_000079.2
COL1A1	XM_011524341.2	c.299-20C>G		intron_variant			XP_011522643.1
COL1A1	XM_005257058.5	c.299-20C>G		intron_variant			XP_005257115.2
COL1A1	XM_005257059.5	c.299-20C>G		intron_variant			XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10	c.299-20C>G		intron_variant		1	NM_000088.4	ENSP00000225964.6
COL1A1	ENST00000507689.1	c.353-20C>G		intron_variant		2		ENSP00000460459.1
COL1A1	ENST00000474644.1	n.418-20C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84198 AN: 151886 Hom.: 25697 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.551

GnomAD3 exomes AF: 0.626 AC: 157107 AN: 250922 Hom.: 50620 AF XY: 0.632 AC XY: 85729 AN XY: 135680

Gnomad AFR exome AF: 0.273

Gnomad AMR exome AF: 0.594

Gnomad ASJ exome AF: 0.642

Gnomad EAS exome AF: 0.622

Gnomad SAS exome AF: 0.606

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.637

GnomAD4 exome AF: 0.660 AC: 964366 AN: 1461410 Hom.: 322222 Cov.: 62 AF XY: 0.660 AC XY: 479498 AN XY: 727018

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.645

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.717

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.554 AC: 84232 AN: 152002 Hom.: 25709 Cov.: 32 AF XY: 0.557 AC XY: 41392 AN XY: 74288

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.551

Alfa AF: 0.619 Hom.: 5592

Bravo AF: 0.529

Asia WGS AF: 0.592 AC: 2061 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2016	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. -

Osteogenesis imperfecta type I Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 04, 2025	- -

Osteogenesis imperfecta type III Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Osteogenesis imperfecta with normal sclerae, dominant form Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Ehlers-Danlos syndrome, arthrochalasia type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Osteogenesis imperfecta, perinatal lethal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
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: rs2256835; hg19: chr17-48276971; COSMIC: COSV56806200; COSMIC: COSV56806200;