Variant 3-98580004-C-T 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_000097.7(CPOX):c.*679G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 984,934 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.031 ( 133 hom., cov: 33)

Exomes 𝑓: 0.013 ( 144 hom. )

Consequence

CPOX
NM_000097.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.290

Variant links:

Genes affected

CPOX (HGNC:2321): (coproporphyrinogen oxidase) The protein encoded by this gene is the sixth enzyme of the heme biosynthetic pathway. The encoded enzyme is soluble and found in the intermembrane space of mitochondria. This enzyme catalyzes the stepwise oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX, a precursor of heme. Defects in this gene are a cause of hereditary coproporphyria (HCP).[provided by RefSeq, Oct 2009]

CPOX 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=-0.77).

BP6

Variant 3-98580004-C-T is Benign according to our data. Variant chr3-98580004-C-T is described in ClinVar as [Benign]. Clinvar id is 346956.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CPOX	NM_000097.7 linkuse as main transcript	c.*679G>A	3_prime_UTR_variant	7/7	ENST00000647941.2	NP_000088.3
CPOX	XM_005247125.5 linkuse as main transcript	c.1173-1734G>A	intron_variant			XP_005247182.1
CPOX	XR_001740025.3 linkuse as main transcript	n.1280-1734G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPOX	ENST00000647941.2 linkuse as main transcript	c.*679G>A		3_prime_UTR_variant	7/7		NM_000097.7	ENSP00000497326	P1	P36551-1

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4664

AN:

152104

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.00769

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.00791

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0369

GnomAD4 exome

AF:

0.0135

AC:

11205

AN:

832712

Hom.:

144

Cov.:

AF XY:

0.0134

AC XY:

5159

AN XY:

384618

show subpopulations

Gnomad4 AFR exome

AF:

0.0844

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.0206

Gnomad4 EAS exome

AF:

0.00552

Gnomad4 SAS exome

AF:

0.0224

Gnomad4 FIN exome

AF:

0.00712

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.0308

AC:

4687

AN:

152222

Hom.:

133

Cov.:

AF XY:

0.0298

AC XY:

2222

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0753

Gnomad4 AMR

AF:

0.0229

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.00771

Gnomad4 SAS

AF:

0.0186

Gnomad4 FIN

AF:

0.00791

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.0365

Alfa

AF:

0.0232

Hom.:

Bravo

AF:

0.0342

Asia WGS

AF:

0.0260

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary coproporphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.5

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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