Variant rs2075556 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000088.4(COL1A1):c.2127+128G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,177,800 control chromosomes in the GnomAD database, including 14,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1747 hom., cov: 33)

Exomes 𝑓: 0.15 ( 12839 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.221

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-50191660-C-G is Benign according to our data. Variant chr17-50191660-C-G is described in ClinVar as [Benign]. Clinvar id is 1291104.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COL1A1	NM_000088.4 linkuse as main transcript	c.2127+128G>C	intron_variant	ENST00000225964.10
COL1A1	XM_005257058.5 linkuse as main transcript	c.2127+128G>C	intron_variant
COL1A1	XM_005257059.5 linkuse as main transcript	c.1209+128G>C	intron_variant
COL1A1	XM_011524341.2 linkuse as main transcript	c.1929+128G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10 linkuse as main transcript	c.2127+128G>C		intron_variant		1	NM_000088.4	P1
COL1A1	ENST00000476387.1 linkuse as main transcript	n.476+128G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22092

AN:

152098

Hom.:

1743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.149

AC:

152521

AN:

1025584

Hom.:

12839

Cov.:

AF XY:

0.153

AC XY:

79673

AN XY:

520722

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.320

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.145

AC:

22100

AN:

152216

Hom.:

1747

Cov.:

AF XY:

0.148

AC XY:

11020

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.161

Alfa

AF:

0.0701

Hom.:

Bravo

AF:

0.143

Asia WGS

AF:

0.294

AC:

1019

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.3

DANN

Benign

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over