rs11079898

Positions:

• chr17-50197263-T-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.697-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,610,468 control chromosomes in the GnomAD database, including 5,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2652 hom., cov: 32)
  • Exomes 𝑓: 0.031 (2954 hom.)
• Consequence: COL1A1 NM_000088.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.41

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=-0.83).
• BP6: Variant 17-50197263-T-C is Benign according to our data. Variant chr17-50197263-T-C is described in ClinVar as [Benign]. Clinvar id is 675133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A1	NM_000088.4	c.697-30A>G		intron_variant		ENST00000225964.10	NP_000079.2
COL1A1	XM_005257058.5	c.697-30A>G		intron_variant			XP_005257115.2
COL1A1	XM_005257059.5	c.697-30A>G		intron_variant			XP_005257116.2
COL1A1	XM_011524341.2	c.697-30A>G		intron_variant			XP_011522643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10	c.697-30A>G		intron_variant		1	NM_000088.4	ENSP00000225964	P1
COL1A1	ENST00000495677.1	n.424-30A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17480 AN: 151958 Hom.: 2639 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.00944

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0837

GnomAD3 exomes AF: 0.0481 AC: 12063 AN: 250750 Hom.: 1198 AF XY: 0.0436 AC XY: 5908 AN XY: 135646

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.0277

Gnomad ASJ exome AF: 0.0223

Gnomad EAS exome AF: 0.00615

Gnomad SAS exome AF: 0.0585

Gnomad FIN exome AF: 0.0142

Gnomad NFE exome AF: 0.0234

Gnomad OTH exome AF: 0.0351

GnomAD4 exome AF: 0.0312 AC: 45572 AN: 1458392 Hom.: 2954 Cov.: 33 AF XY: 0.0314 AC XY: 22763 AN XY: 725658

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.0217

Gnomad4 EAS exome AF: 0.00640

Gnomad4 SAS exome AF: 0.0595

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.0201

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.115 AC: 17522 AN: 152076 Hom.: 2652 Cov.: 32 AF XY: 0.112 AC XY: 8344 AN XY: 74336

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.0478

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.00927

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0630 Hom.: 214

Bravo AF: 0.127

Asia WGS AF: 0.0520 AC: 180 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	-0.83
CADD	Benign	0.49
DANN	Benign	0.33

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: rs11079898; hg19: chr17-48274624; COSMIC: COSV56806377; COSMIC: COSV56806377;