NM_000097.7:c.1172+1103C>T

Variant names:

• chr3-98584338-G-A
• rs3804622
• NM_000097.7:c.1172+1103C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

ENSG00000285635 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CPOX	NM_000097.7	c.1172+1103C>T		intron_variant	Intron 5 of 6	ENST00000647941.2	NP_000088.3
CPOX	XM_005247125.5	c.1172+1103C>T		intron_variant	Intron 5 of 5		XP_005247182.1
CPOX	XR_001740025.3	n.1279+1103C>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPOX	ENST00000647941.2	c.1172+1103C>T		intron_variant	Intron 5 of 6		NM_000097.7	ENSP00000497326.1
ENSG00000285635	ENST00000512905.6	n.56+1103C>T		intron_variant	Intron 1 of 3	5		ENSP00000425880.1
CPOX	ENST00000510489.1	n.422+1103C>T		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.249 AC: 10312 AN: 41450

American (AMR) AF: 0.506 AC: 7728 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2067 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2779 AN: 5152

South Asian (SAS) AF: 0.525 AC: 2530 AN: 4816

European-Finnish (FIN) AF: 0.467 AC: 4918 AN: 10538

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35731 AN: 67930

Other (OTH) AF: 0.466 AC: 981 AN: 2106

Alfa AF: 0.506 Hom.: 76159

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
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3804622; hg19: chr3-98303182;