18-57568045-T-C

Position:

• chr18-57568045-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.464-1464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,112 control chromosomes in the GnomAD database, including 31,736 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 0.64 (31736 hom., cov: 33)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5	c.464-1464A>G		intron_variant		ENST00000262093.11	NP_000131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11	c.464-1464A>G		intron_variant		1	NM_000140.5	ENSP00000262093.6

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97801 AN: 151994 Hom.: 31713 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.644 AC: 97890 AN: 152112 Hom.: 31736 Cov.: 33 AF XY: 0.640 AC XY: 47546 AN XY: 74342

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.628

Alfa AF: 0.587 Hom.: 3600

Bravo AF: 0.654

Asia WGS AF: 0.648 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.45

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: rs1790619; hg19: chr18-55235277;