rs41316671

Positions:

• chr17-50192756-C-G

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.1875+41G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,614,036 control chromosomes in the GnomAD database, including 530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (75 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (455 hom.)
• Consequence: COL1A1 NM_000088.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0690

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]

COL1A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-50192756-C-G is Benign according to our data. Variant chr17-50192756-C-G is described in ClinVar as [Benign]. Clinvar id is 679029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A1	NM_000088.4	c.1875+41G>C		intron_variant		ENST00000225964.10	NP_000079.2
COL1A1	XM_011524341.2	c.1677+41G>C		intron_variant			XP_011522643.1
COL1A1	XM_005257058.5	c.1875+41G>C		intron_variant			XP_005257115.2
COL1A1	XM_005257059.5	c.958-63G>C		intron_variant			XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10	c.1875+41G>C		intron_variant		1	NM_000088.4	ENSP00000225964.6
COL1A1	ENST00000476387.1	n.224+41G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2357 AN: 152140 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.0217 AC: 5452 AN: 251266 Hom.: 223 AF XY: 0.0200 AC XY: 2716 AN XY: 135842

Gnomad AFR exome AF: 0.0282

Gnomad AMR exome AF: 0.0455

Gnomad ASJ exome AF: 0.0155

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.0289

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.0129

GnomAD4 exome AF: 0.00782 AC: 11426 AN: 1461776 Hom.: 455 Cov.: 35 AF XY: 0.00812 AC XY: 5906 AN XY: 727196

Gnomad4 AFR exome AF: 0.0266

Gnomad4 AMR exome AF: 0.0456

Gnomad4 ASJ exome AF: 0.0151

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0289

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000227

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0156 AC: 2373 AN: 152260 Hom.: 75 Cov.: 32 AF XY: 0.0164 AC XY: 1220 AN XY: 74446

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0276

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0336

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00893 Hom.: 6

Bravo AF: 0.0190

Asia WGS AF: 0.0820 AC: 283 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 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	-0.80
CADD	Benign	5.5
DANN	Benign	0.50

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: rs41316671; hg19: chr17-48270117; COSMIC: COSV56805673; COSMIC: COSV56805673;