Genetic Variant CPOX:c.*578_*579insTTCTTA (chr3-98580104-T-TTAAGAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000097.7(CPOX):c.*578_*579insTTCTTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.78 ( 46688 hom., cov: 0)

Exomes 𝑓: 0.75 ( 231663 hom. )

Consequence

CPOX
NM_000097.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.369

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

CPOX-related hereditary coproporphyria
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
hereditary coproporphyria
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
harderoporphyria
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp

CPOX links:

ENSG00000285635 (HGNC:):

ENSG00000285635 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 3-98580104-T-TTAAGAA is Benign according to our data. Variant chr3-98580104-T-TTAAGAA is described in ClinVar as [Benign]. Clinvar id is 346958.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CPOX	NM_000097.7 link	c.578_579insTTCTTA	3_prime_UTR_variant	Exon 7 of 7	ENST00000647941.2	NP_000088.3	P36551-1
CPOX	XM_005247125.5 link	c.1173-1835_1173-1834insTTCTTA	intron_variant	Intron 5 of 5		XP_005247182.1
CPOX	XR_001740025.3 link	n.1280-1835_1280-1834insTTCTTA	intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPOX	ENST00000647941.2 link	c.578_579insTTCTTA		3_prime_UTR_variant	Exon 7 of 7		NM_000097.7	ENSP00000497326.1		P36551-1
ENSG00000285635	ENST00000512905.6 link	n.161+1302_161+1303insTTCTTA		intron_variant	Intron 2 of 3	5		ENSP00000425880.1		H0YA22

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118244

AN:

151364

Hom.:

46651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.899

Gnomad AMI

AF:

0.682

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.634

Gnomad FIN

AF:

0.791

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.772

GnomAD4 exome

AF:

0.749

AC:

617277

AN:

824524

Hom.:

231663

Cov.:

AF XY:

0.748

AC XY:

285426

AN XY:

381354

show subpopulations

African (AFR)

AF:

0.916

AC:

14217

AN:

15514

American (AMR)

AF:

0.674

AC:

658

AN:

976

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

3970

AN:

5082

East Asian (EAS)

AF:

0.694

AC:

2494

AN:

3592

South Asian (SAS)

AF:

0.636

AC:

10358

AN:

16290

European-Finnish (FIN)

AF:

0.768

AC:

458

AN:

596

Middle Eastern (MID)

AF:

0.792

AC:

1274

AN:

1608

European-Non Finnish (NFE)

AF:

0.748

AC:

563924

AN:

753886

Other (OTH)

AF:

0.738

AC:

19924

AN:

26980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

7666

15333

22999

30666

38332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.781

AC:

118325

AN:

151486

Hom.:

46688

Cov.:

AF XY:

0.777

AC XY:

57457

AN XY:

73962

show subpopulations

African (AFR)

AF:

0.899

AC:

37208

AN:

41370

American (AMR)

AF:

0.677

AC:

10324

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

2646

AN:

3458

East Asian (EAS)

AF:

0.660

AC:

3392

AN:

5136

South Asian (SAS)

AF:

0.635

AC:

3050

AN:

4804

European-Finnish (FIN)

AF:

0.791

AC:

8282

AN:

10466

Middle Eastern (MID)

AF:

0.806

AC:

232

AN:

288

European-Non Finnish (NFE)

AF:

0.753

AC:

50960

AN:

67708

Other (OTH)

AF:

0.765

AC:

1616

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1298

2595

3893

5190

6488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.672

Hom.:

1542

Asia WGS

AF:

0.654

AC:

2271

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary coproporphyria

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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3-98580104-T-TTAAGAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over