Variant 3-98580354-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_StrongBS1BS2

The NM_000097.7(CPOX):c.*329G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,012,022 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 68 hom., cov: 33)

Exomes 𝑓: 0.013 ( 117 hom. )

Consequence

CPOX
NM_000097.7 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

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:

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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=-0.86).

BP6

Variant 3-98580354-C-G is Benign according to our data. Variant chr3-98580354-C-G is described in ClinVar as [Benign]. Clinvar id is 346964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0229 (3482/152172) while in subpopulation AFR AF= 0.0482 (1999/41516). AF 95% confidence interval is 0.0464. There are 68 homozygotes in gnomad4. There are 1636 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 68 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CPOX	NM_000097.7 linkuse as main transcript	c.*329G>C	3_prime_UTR_variant	7/7	ENST00000647941.2	NP_000088.3
CPOX	XM_005247125.5 linkuse as main transcript	c.1173-2084G>C	intron_variant			XP_005247182.1
CPOX	XR_001740025.3 linkuse as main transcript	n.1280-2084G>C	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.*329G>C		3_prime_UTR_variant	7/7		NM_000097.7	ENSP00000497326	P1	P36551-1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3483

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00770

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.00794

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.0311

GnomAD4 exome

AF:

0.0128

AC:

10996

AN:

859850

Hom.:

117

Cov.:

AF XY:

0.0129

AC XY:

5136

AN XY:

398966

show subpopulations

Gnomad4 AFR exome

AF:

0.0526

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.0101

Gnomad4 SAS exome

AF:

0.0222

Gnomad4 FIN exome

AF:

0.00427

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.0168

GnomAD4 genome

AF:

0.0229

AC:

3482

AN:

152172

Hom.:

Cov.:

AF XY:

0.0220

AC XY:

1636

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0482

Gnomad4 AMR

AF:

0.0195

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.00772

Gnomad4 SAS

AF:

0.0184

Gnomad4 FIN

AF:

0.00794

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.00700

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary coproporphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

-0.86

CADD

Benign

0.43

DANN

Benign

0.62

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