rs3804622

chr3-98584338-G-Achr3-98584338-G-Cchr3-98584338-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000097.7(CPOX):c.1172+1103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,926 control chromosomes in the GnomAD database, including 16,322 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16322 hom., cov: 31)
• Consequence: CPOX NM_000097.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPOX	NM_000097.7	c.1172+1103C>T		intron_variant		ENST00000647941.2
CPOX	XM_005247125.5	c.1172+1103C>T		intron_variant
CPOX	XR_001740025.3	n.1279+1103C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPOX	ENST00000647941.2	c.1172+1103C>T		intron_variant			NM_000097.7	P1
CPOX	ENST00000510489.1	n.422+1103C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67610 AN: 151808 Hom.: 16315 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.467

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67640 AN: 151926 Hom.: 16322 Cov.: 31 AF XY: 0.447 AC XY: 33152 AN XY: 74238

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.466

Alfa AF: 0.518 Hom.: 34271

Bravo AF: 0.441

Asia WGS AF: 0.521 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.8
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs3804622; hg19: chr3-98303182;