chr18-57583032-T-C

Position:

• chr18-57583032-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.68-2833A>G		intron_variant		ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.68-2833A>G		intron_variant		1	NM_000140.5

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

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.728

Alfa AF: 0.681 Hom.: 72274

Bravo AF: 0.729

Asia WGS AF: 0.859 AC: 2983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.61

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: rs317806; hg19: chr18-55250264;