Variant 19-18790809-C-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.165+41G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,558,104 control chromosomes in the GnomAD database, including 9,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2321 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7623 hom. )

Consequence

COMP
NM_000095.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.590

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 19-18790809-C-G is Benign according to our data. Variant chr19-18790809-C-G is described in ClinVar as [Benign]. Clinvar id is 255118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COMP	NM_000095.3 linkuse as main transcript	c.165+41G>C		intron_variant		ENST00000222271.7	NP_000086.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
COMP	ENST00000222271.7 linkuse as main transcript	c.165+41G>C	intron_variant	1	NM_000095.3	ENSP00000222271	P1	P49747-1
COMP	ENST00000542601.6 linkuse as main transcript	c.66+41G>C	intron_variant	1		ENSP00000439156
COMP	ENST00000425807.1 linkuse as main transcript	c.165+41G>C	intron_variant	2		ENSP00000403792		P49747-2

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22223

AN:

152086

Hom.:

2310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0857

Gnomad ASJ

AF:

0.0773

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0991

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.0849

AC:

13525

AN:

159334

Hom.:

890

AF XY:

0.0809

AC XY:

7051

AN XY:

87106

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.0481

Gnomad ASJ exome

AF:

0.0824

Gnomad EAS exome

AF:

0.00546

Gnomad SAS exome

AF:

0.0263

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0803

GnomAD4 exome

AF:

0.0958

AC:

134656

AN:

1405900

Hom.:

7623

Cov.:

AF XY:

0.0930

AC XY:

64739

AN XY:

695836

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.0518

Gnomad4 ASJ exome

AF:

0.0843

Gnomad4 EAS exome

AF:

0.00865

Gnomad4 SAS exome

AF:

0.0246

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.0984

Gnomad4 OTH exome

AF:

0.0935

GnomAD4 genome

AF:

0.146

AC:

22267

AN:

152204

Hom.:

2321

Cov.:

AF XY:

0.142

AC XY:

10604

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.0855

Gnomad4 ASJ

AF:

0.0773

Gnomad4 EAS

AF:

0.00561

Gnomad4 SAS

AF:

0.0244

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.0991

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.113

Hom.:

230

Bravo

AF:

0.150

Asia WGS

AF:

0.0420

AC:

145

AN:

3476

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.7

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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