Variant 19-18783036-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000095.3(COMP):c.2227+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000955 in 1,612,050 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

COMP
NM_000095.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.40

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-18783036-C-T is Benign according to our data. Variant chr19-18783036-C-T is described in ClinVar as [Benign]. Clinvar id is 1565069.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-18783036-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000459 (70/152340) while in subpopulation AFR AF= 0.00166 (69/41584). AF 95% confidence interval is 0.00134. There are 1 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMP	NM_000095.3 linkuse as main transcript	c.2227+18G>A		intron_variant		ENST00000222271.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
COMP	ENST00000222271.7 linkuse as main transcript	c.2227+18G>A	intron_variant	1	NM_000095.3	P1	P49747-1
COMP	ENST00000542601.6 linkuse as main transcript	c.2128+18G>A	intron_variant	1
COMP	ENST00000425807.1 linkuse as main transcript	c.2068+18G>A	intron_variant	2			P49747-2

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000885

AC:

AN:

248584

Hom.:

AF XY:

0.0000742

AC XY:

AN XY:

134844

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000575

AC:

AN:

1459710

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726216

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000459

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.000465

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

Invitae

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.024

DANN

Benign

0.44

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