18-57545084-G-T

Position:

• chr18-57545084-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000140.5(FECH):​c.*5628C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,964 control chromosomes in the GnomAD database, including 10,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (10054 hom., cov: 32)
• Consequence: FECH NM_000140.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.80

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-57545084-G-T is Benign according to our data. Variant chr18-57545084-G-T is described in ClinVar as [Benign]. Clinvar id is 327316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.*5628C>A		3_prime_UTR_variant	11/11	ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.*5628C>A		3_prime_UTR_variant	11/11	1	NM_000140.5
FECH	ENST00000652755.1	c.*5628C>A		3_prime_UTR_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49684 AN: 151846 Hom.: 10055 Cov.: 32

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.327 AC: 49674 AN: 151964 Hom.: 10054 Cov.: 32 AF XY: 0.319 AC XY: 23659 AN XY: 74252

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.353

Alfa AF: 0.353 Hom.: 1984

Bravo AF: 0.311

Asia WGS AF: 0.230 AC: 803 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
CADD	Benign	0.081
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13732; hg19: chr18-55212316;