3-98580104-T-TTAAGAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.369

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
CPOX	NM_000097.7	c.*578_*579insTTCTTA		3_prime_UTR_variant	7/7	ENST00000647941.2
CPOX	XM_005247125.5	c.1173-1835_1173-1834insTTCTTA		intron_variant
CPOX	XR_001740025.3	n.1280-1835_1280-1834insTTCTTA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPOX	ENST00000647941.2	c.*578_*579insTTCTTA		3_prime_UTR_variant	7/7		NM_000097.7	P1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118244 AN: 151364 Hom.: 46651 Cov.: 0

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.: 20 AF XY: 0.748 AC XY: 285426 AN XY: 381354

Gnomad4 AFR exome AF: 0.916

Gnomad4 AMR exome AF: 0.674

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 0.694

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.768

Gnomad4 NFE exome AF: 0.748

Gnomad4 OTH exome AF: 0.738

GnomAD4 genome AF: 0.781 AC: 118325 AN: 151486 Hom.: 46688 Cov.: 0 AF XY: 0.777 AC XY: 57457 AN XY: 73962

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.765

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

Submissions by phenotype

Hereditary coproporphyria Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3840202; hg19: chr3-98298948;