Variant 17-50196948-T-C 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.804+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 1,573,952 control chromosomes in the GnomAD database, including 560,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.81 ( 50025 hom., cov: 32)

Exomes 𝑓: 0.85 ( 510550 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.52

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=-0.91).

BP6

Variant 17-50196948-T-C is Benign according to our data. Variant chr17-50196948-T-C is described in ClinVar as [Benign]. Clinvar id is 674976.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COL1A1	NM_000088.4 linkuse as main transcript	c.804+62A>G	intron_variant	ENST00000225964.10
COL1A1	XM_005257058.5 linkuse as main transcript	c.804+62A>G	intron_variant
COL1A1	XM_005257059.5 linkuse as main transcript	c.804+62A>G	intron_variant
COL1A1	XM_011524341.2 linkuse as main transcript	c.804+62A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10 linkuse as main transcript	c.804+62A>G		intron_variant		1	NM_000088.4	P1
COL1A1	ENST00000495677.1 linkuse as main transcript	n.531+62A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.808

AC:

122831

AN:

152032

Hom.:

50001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.890

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.865

Gnomad OTH

AF:

0.802

GnomAD4 exome

AF:

0.845

AC:

1201428

AN:

1421802

Hom.:

510550

AF XY:

0.842

AC XY:

597642

AN XY:

709766

show subpopulations

Gnomad4 AFR exome

AF:

0.732

Gnomad4 AMR exome

AF:

0.710

Gnomad4 ASJ exome

AF:

0.851

Gnomad4 EAS exome

AF:

0.631

Gnomad4 SAS exome

AF:

0.733

Gnomad4 FIN exome

AF:

0.876

Gnomad4 NFE exome

AF:

0.870

Gnomad4 OTH exome

AF:

0.837

GnomAD4 genome

AF:

0.808

AC:

122907

AN:

152150

Hom.:

50025

Cov.:

AF XY:

0.805

AC XY:

59843

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.733

Gnomad4 AMR

AF:

0.751

Gnomad4 ASJ

AF:

0.856

Gnomad4 EAS

AF:

0.672

Gnomad4 SAS

AF:

0.738

Gnomad4 FIN

AF:

0.890

Gnomad4 NFE

AF:

0.865

Gnomad4 OTH

AF:

0.800

Alfa

AF:

0.850

Hom.:

20324

Bravo

AF:

0.794

Asia WGS

AF:

0.689

AC:

2400

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 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

-0.91

CADD

Benign

2.1

DANN

Benign

0.53

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