rs8339

chr18-57550464-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000140.5(FECH):c.*248C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 466,038 control chromosomes in the GnomAD database, including 11,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4835 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6313 hom.)
• Consequence: FECH NM_000140.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.157

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 18-57550464-G-A is Benign according to our data. Variant chr18-57550464-G-A is described in ClinVar as [Benign]. Clinvar id is 327419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.*248C>T		3_prime_UTR_variant	11/11	ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.*248C>T		3_prime_UTR_variant	11/11	1	NM_000140.5

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33238 AN: 151986 Hom.: 4825 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.169 AC: 53073 AN: 313934 Hom.: 6313 Cov.: 4 AF XY: 0.170 AC XY: 28051 AN XY: 164694

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.219 AC: 33304 AN: 152104 Hom.: 4835 Cov.: 32 AF XY: 0.221 AC XY: 16426 AN XY: 74362

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.224

Alfa AF: 0.143 Hom.: 1097

Bravo AF: 0.240

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Protoporphyria, erythropoietic, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.087
Dann	Benign	0.34

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: rs8339; hg19: chr18-55217696;