Variant rs12327738 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.1915-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,609,758 control chromosomes in the GnomAD database, including 75,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6554 hom., cov: 31)

Exomes 𝑓: 0.30 ( 68460 hom. )

Consequence

COMP
NM_000095.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.25

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=-0.91).

BP6

Variant 19-18784408-G-A is Benign according to our data. Variant chr19-18784408-G-A is described in ClinVar as [Benign]. Clinvar id is 255121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 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.1915-45C>T		intron_variant		ENST00000222271.7	NP_000086.2	P49747-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COMP	ENST00000222271.7 linkuse as main transcript	c.1915-45C>T	intron_variant	1	NM_000095.3	ENSP00000222271.2	P49747-1
COMP	ENST00000542601.6 linkuse as main transcript	c.1816-45C>T	intron_variant	1		ENSP00000439156.2	G3XAP6
COMP	ENST00000425807.1 linkuse as main transcript	c.1756-45C>T	intron_variant	2		ENSP00000403792.1	P49747-2

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43388

AN:

151926

Hom.:

6555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.0988

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.269

AC:

66307

AN:

246460

Hom.:

9570

AF XY:

0.267

AC XY:

35763

AN XY:

133926

show subpopulations

Gnomad AFR exome

AF:

0.253

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.0965

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.396

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.300

AC:

437198

AN:

1457714

Hom.:

68460

Cov.:

AF XY:

0.296

AC XY:

214492

AN XY:

725212

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.0906

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.399

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.285

AC:

43389

AN:

152044

Hom.:

6554

Cov.:

AF XY:

0.283

AC XY:

21063

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.245

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.0988

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.403

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.297

Hom.:

1421

Bravo

AF:

0.270

Asia WGS

AF:

0.133

AC:

464

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.032

DANN

Benign

0.55

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