Variant 19-18783001-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000095.3(COMP):c.2228-40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,611,948 control chromosomes in the GnomAD database, including 24,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4092 hom., cov: 33)

Exomes 𝑓: 0.16 ( 20114 hom. )

Consequence

COMP
NM_000095.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.15

Variant links:

Genes affected

COMP (HGNC:2227): (cartilage oligomeric matrix protein) The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfides. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Contraction or expansion of a 5 aa aspartate repeat and other mutations can cause pseudochondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). [provided by RefSeq, Jul 2016]

COMP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-18783001-A-G is Benign according to our data. Variant chr19-18783001-A-G is described in ClinVar as [Benign]. Clinvar id is 255123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMP	NM_000095.3 linkuse as main transcript	c.2228-40T>C		intron_variant		ENST00000222271.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
COMP	ENST00000222271.7 linkuse as main transcript	c.2228-40T>C	intron_variant	1	NM_000095.3	P1	P49747-1
COMP	ENST00000542601.6 linkuse as main transcript	c.2129-40T>C	intron_variant	1
COMP	ENST00000425807.1 linkuse as main transcript	c.2069-40T>C	intron_variant	2			P49747-2

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32253

AN:

152080

Hom.:

4074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.0982

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.166

AC:

41203

AN:

248552

Hom.:

3892

AF XY:

0.164

AC XY:

22146

AN XY:

134888

show subpopulations

Gnomad AFR exome

AF:

0.362

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.188

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.0998

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.161

AC:

235199

AN:

1459748

Hom.:

20114

Cov.:

AF XY:

0.162

AC XY:

117707

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.371

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.212

AC:

32316

AN:

152200

Hom.:

4092

Cov.:

AF XY:

0.208

AC XY:

15463

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.185

Gnomad4 FIN

AF:

0.0982

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.128

Hom.:

341

Bravo

AF:

0.224

Asia WGS

AF:

0.208

AC:

722

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.090

DANN

Benign

0.28

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