chr18-57583032-T-C

Variant names:

• chr18-57583032-T-C
• rs317806
• NM_000140.5:c.68-2833A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000140.5(FECH):​c.68-2833A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,884 control chromosomes in the GnomAD database, including 39,772 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 0.72 (39772 hom., cov: 30)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 13 publications found

Genes affected

FECH (HGNC:3647): (ferrochelatase) The protein encoded by this gene is localized to the mitochondrion, where it catalyzes the insertion of the ferrous form of iron into protoporphyrin IX in the heme synthesis pathway. Mutations in this gene are associated with erythropoietic protoporphyria. Two transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome 3.[provided by RefSeq, May 2010]

FECH Gene-Disease associations (from GenCC):

• protoporphyria, erythropoietic, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae)
• autosomal erythropoietic protoporphyria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000140.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FECH	NM_000140.5	MANE Select	c.68-2833A>G		intron	N/A	NP_000131.2
	FECH	NM_001012515.4		c.68-2833A>G		intron	N/A	NP_001012533.1
	FECH	NM_001374778.1		c.68-2833A>G		intron	N/A	NP_001361707.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FECH	ENST00000262093.11	TSL:1 MANE Select	c.68-2833A>G		intron	N/A	ENSP00000262093.6
	FECH	ENST00000652755.1		c.68-2833A>G		intron	N/A	ENSP00000498358.1
	FECH	ENST00000382873.8	TSL:2	c.-150+2832A>G		intron	N/A	ENSP00000372326.4

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109294 AN: 151766 Hom.: 39730 Cov.: 30

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.720 AC: 109398 AN: 151884 Hom.: 39772 Cov.: 30 AF XY: 0.722 AC XY: 53552 AN XY: 74182

African (AFR) AF: 0.780 AC: 32272 AN: 41372

American (AMR) AF: 0.737 AC: 11245 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2345 AN: 3468

East Asian (EAS) AF: 0.986 AC: 5097 AN: 5168

South Asian (SAS) AF: 0.745 AC: 3587 AN: 4814

European-Finnish (FIN) AF: 0.668 AC: 7034 AN: 10528

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45437 AN: 67952

Other (OTH) AF: 0.728 AC: 1537 AN: 2110

Alfa AF: 0.686 Hom.: 150866

Bravo AF: 0.729

Asia WGS AF: 0.859 AC: 2983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.61
PhyloP100		-0.26
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: rs317806; hg19: chr18-55250264;