17-50189930-G-C

Position:

• chr17-50189930-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.2560-18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,612,158 control chromosomes in the GnomAD database, including 214,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (20984 hom., cov: 32)
  • Exomes 𝑓: 0.51 (193701 hom.)
• Consequence: COL1A1 NM_000088.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.929

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=-0.77).
• BP6: Variant 17-50189930-G-C is Benign according to our data. Variant chr17-50189930-G-C is described in ClinVar as [Benign]. Clinvar id is 254948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50189930-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A1	NM_000088.4	c.2560-18C>G		intron_variant		ENST00000225964.10	NP_000079.2
COL1A1	XM_011524341.2	c.2362-18C>G		intron_variant			XP_011522643.1
COL1A1	XM_005257058.5	c.2560-18C>G		intron_variant			XP_005257115.2
COL1A1	XM_005257059.5	c.1642-18C>G		intron_variant			XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10	c.2560-18C>G		intron_variant		1	NM_000088.4	ENSP00000225964.6

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79741 AN: 151782 Hom.: 20969 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.520

GnomAD3 exomes AF: 0.522 AC: 129504 AN: 248000 Hom.: 34255 AF XY: 0.517 AC XY: 69401 AN XY: 134152

Gnomad AFR exome AF: 0.553

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.524

Gnomad EAS exome AF: 0.521

Gnomad SAS exome AF: 0.518

Gnomad FIN exome AF: 0.454

Gnomad NFE exome AF: 0.496

Gnomad OTH exome AF: 0.517

GnomAD4 exome AF: 0.513 AC: 749573 AN: 1460256 Hom.: 193701 Cov.: 52 AF XY: 0.512 AC XY: 371807 AN XY: 726348

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.525 AC: 79793 AN: 151902 Hom.: 20984 Cov.: 32 AF XY: 0.525 AC XY: 38965 AN XY: 74238

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.519

Alfa AF: 0.430 Hom.: 2113

Bravo AF: 0.541

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 26, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Osteogenesis imperfecta type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.69

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: rs2075559; hg19: chr17-48267291; COSMIC: COSV56805103; COSMIC: COSV56805103;