rs1057523677

Variant names:

• chr17-50199886-G-A
• rs1057523677
• NM_000088.4:c.165C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-50199886-G-A
• chr17-50199886-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000088.4(COL1A1):​c.165C>T​(p.Pro55Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL1A1 NM_000088.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.247

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]

ENSG00000249406 (HGNC:52795): (long intergenic non-protein coding RNA 1969)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 17-50199886-G-A is Benign according to our data. Variant chr17-50199886-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 390205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.247 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4	c.165C>T	p.Pro55Pro	synonymous_variant	Exon 2 of 51	ENST00000225964.10	NP_000079.2
COL1A1	XM_011524341.2	c.165C>T	p.Pro55Pro	synonymous_variant	Exon 2 of 48		XP_011522643.1
COL1A1	XM_005257058.5	c.165C>T	p.Pro55Pro	synonymous_variant	Exon 2 of 49		XP_005257115.2
COL1A1	XM_005257059.5	c.165C>T	p.Pro55Pro	synonymous_variant	Exon 2 of 38		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10	c.165C>T	p.Pro55Pro	synonymous_variant	Exon 2 of 51	1	NM_000088.4	ENSP00000225964.6
COL1A1	ENST00000507689.1	c.219C>T	p.Pro73Pro	synonymous_variant	Exon 1 of 4	2		ENSP00000460459.1
COL1A1	ENST00000474644.1	n.284C>T		non_coding_transcript_exon_variant	Exon 2 of 4	3
ENSG00000249406	ENST00000509943.2	n.11G>A		non_coding_transcript_exon_variant	Exon 1 of 7	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 24, 2016

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.43
CADD	Benign	17
DANN	Benign	0.96

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: rs1057523677; hg19: chr17-48277247;