chr17-50199874-C-A

Variant names:

• chr17-50199874-C-A
• rs1057297
• NM_000088.4:c.177G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000088.4(COL1A1):​c.177G>T​(p.Arg59Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,614,152 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (238 hom., cov: 33)
  • Exomes 𝑓: 0.015 (412 hom.)
• Consequence: COL1A1 NM_000088.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.928
• Publications: 10 publications found

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]

TILAM (HGNC:52795): (long intergenic non-protein coding RNA 1969)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 17-50199874-C-A is Benign according to our data. Variant chr17-50199874-C-A is described in ClinVar as Benign. ClinVar VariationId is 254945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.928 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000088.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL1A1	NM_000088.4	MANE Select	c.177G>T	p.Arg59Arg	synonymous	Exon 2 of 51	NP_000079.2	P02452

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL1A1	ENST00000225964.10	TSL:1 MANE Select	c.177G>T	p.Arg59Arg	synonymous	Exon 2 of 51	ENSP00000225964.6	P02452
	COL1A1	ENST00000861334.1		c.177G>T	p.Arg59Arg	synonymous	Exon 2 of 51	ENSP00000531393.1
	COL1A1	ENST00000861339.1		c.177G>T	p.Arg59Arg	synonymous	Exon 2 of 51	ENSP00000531398.1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5830 AN: 152160 Hom.: 238 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0384

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.0206 AC: 5168 AN: 251368 AF XY: 0.0201

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.0172

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0116

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.0148

GnomAD4 exome AF: 0.0148 AC: 21605 AN: 1461874 Hom.: 412 Cov.: 35 AF XY: 0.0154 AC XY: 11198 AN XY: 727230

African (AFR) AF: 0.106 AC: 3544 AN: 33480

American (AMR) AF: 0.0106 AC: 475 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 435 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.0391 AC: 3372 AN: 86256

European-Finnish (FIN) AF: 0.0114 AC: 610 AN: 53414

Middle Eastern (MID) AF: 0.0198 AC: 114 AN: 5764

European-Non Finnish (NFE) AF: 0.0107 AC: 11863 AN: 1112008

Other (OTH) AF: 0.0196 AC: 1186 AN: 60392

GnomAD4 genome AF: 0.0384 AC: 5841 AN: 152278 Hom.: 238 Cov.: 33 AF XY: 0.0374 AC XY: 2785 AN XY: 74460

African (AFR) AF: 0.107 AC: 4430 AN: 41548

American (AMR) AF: 0.0151 AC: 231 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0384 AC: 185 AN: 4814

European-Finnish (FIN) AF: 0.0106 AC: 113 AN: 10622

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 743 AN: 68018

Other (OTH) AF: 0.0284 AC: 60 AN: 2112

Alfa AF: 0.0208 Hom.: 173

Bravo AF: 0.0405

Asia WGS AF: 0.0250 AC: 85 AN: 3478

EpiCase AF: 0.0111

EpiControl AF: 0.0108

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Osteogenesis imperfecta (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Ehlers-Danlos syndrome (1)
-	-	1	Ehlers-Danlos syndrome, arthrochalasia type (1)
-	-	1	Infantile cortical hyperostosis (1)
-	-	1	Osteogenesis imperfecta type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		0.93
PromoterAI		-0.069	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1057297; hg19: chr17-48277235; COSMIC: COSV56806402;