Variant 18-57554416-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000140.5(FECH):c.921A>G(p.Pro307=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 1,613,744 control chromosomes in the GnomAD database, including 400,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 43324 hom., cov: 32)

Exomes 𝑓: 0.70 ( 357666 hom. )

Consequence

FECH
NM_000140.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.01

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 18-57554416-T-C is Benign according to our data. Variant chr18-57554416-T-C is described in ClinVar as [Benign]. Clinvar id is 255312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-57554416-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5 linkuse as main transcript	c.921A>G	p.Pro307=	synonymous_variant	9/11	ENST00000262093.11	NP_000131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11 linkuse as main transcript	c.921A>G	p.Pro307=	synonymous_variant	9/11	1	NM_000140.5	ENSP00000262093		P22830-1

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

113061

AN:

152018

Hom.:

43283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.927

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.661

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.689

Gnomad OTH

AF:

0.717

GnomAD3 exomes

AF:

0.692

AC:

174013

AN:

251442

Hom.:

61272

AF XY:

0.693

AC XY:

94186

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.935

Gnomad AMR exome

AF:

0.624

Gnomad ASJ exome

AF:

0.710

Gnomad EAS exome

AF:

0.664

Gnomad SAS exome

AF:

0.755

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.691

Gnomad OTH exome

AF:

0.675

GnomAD4 exome

AF:

0.697

AC:

1019045

AN:

1461608

Hom.:

357666

Cov.:

AF XY:

0.698

AC XY:

507639

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.938

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.712

Gnomad4 EAS exome

AF:

0.679

Gnomad4 SAS exome

AF:

0.754

Gnomad4 FIN exome

AF:

0.559

Gnomad4 NFE exome

AF:

0.695

Gnomad4 OTH exome

AF:

0.708

GnomAD4 genome

AF:

0.744

AC:

113163

AN:

152136

Hom.:

43324

Cov.:

AF XY:

0.739

AC XY:

54943

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.927

Gnomad4 AMR

AF:

0.687

Gnomad4 ASJ

AF:

0.710

Gnomad4 EAS

AF:

0.661

Gnomad4 SAS

AF:

0.751

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.715

Alfa

AF:

0.693

Hom.:

50977

Bravo

AF:

0.758

Asia WGS

AF:

0.704

AC:

2446

AN:

3476

EpiCase

AF:

0.680

EpiControl

AF:

0.685

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Protoporphyria, erythropoietic, 1

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.19

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over