18-57567778-G-T

Position:

• chr18-57567778-G-T

Variant summary

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

The NM_000140.5(FECH):​c.464-1197C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,096 control chromosomes in the GnomAD database, including 27,062 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 0.59 (27059 hom., cov: 33)
  • Exomes 𝑓: 0.60 (3 hom.)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5	c.464-1197C>A		intron_variant		ENST00000262093.11	NP_000131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11	c.464-1197C>A		intron_variant		1	NM_000140.5	ENSP00000262093.6

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90197 AN: 151958 Hom.: 27042 Cov.: 33

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.600 AC: 12 AN: 20 Hom.: 3 AF XY: 0.667 AC XY: 8 AN XY: 12

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.594 AC: 90276 AN: 152076 Hom.: 27059 Cov.: 33 AF XY: 0.590 AC XY: 43893 AN XY: 74340

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.595

Alfa AF: 0.607 Hom.: 3482

Bravo AF: 0.598

Asia WGS AF: 0.615 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.021
DANN	Benign	0.54

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: rs7241377; hg19: chr18-55235010;