chr18-57554416-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000140.5(FECH):c.921A>G(p.Pro307Pro) 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

Publications

28 publications found

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 Gene-Disease associations (from GenCC):

protoporphyria, erythropoietic, 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae)
autosomal erythropoietic protoporphyria
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FECH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 255312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
FECH	NM_000140.5 link	c.921A>G	p.Pro307Pro	synonymous_variant	Exon 9 of 11	ENST00000262093.11	NP_000131.2	P22830-1Q7KZA3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11 link	c.921A>G	p.Pro307Pro	synonymous_variant	Exon 9 of 11	1	NM_000140.5	ENSP00000262093.6		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

GnomAD2 exomes

AF:

0.692

AC:

174013

AN:

251442

AF XY:

0.693

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 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

African (AFR)

AF:

0.938

AC:

31409

AN:

33476

American (AMR)

AF:

0.633

AC:

28329

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

18597

AN:

26132

East Asian (EAS)

AF:

0.679

AC:

26963

AN:

39700

South Asian (SAS)

AF:

0.754

AC:

64991

AN:

86252

European-Finnish (FIN)

AF:

0.559

AC:

29856

AN:

53410

Middle Eastern (MID)

AF:

0.656

AC:

3784

AN:

5766

European-Non Finnish (NFE)

AF:

0.695

AC:

772387

AN:

1111768

Other (OTH)

AF:

0.708

AC:

42729

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17788

35575

53363

71150

88938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19680

39360

59040

78720

98400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.744

AC:

113163

AN:

152136

Hom.:

43324

Cov.:

AF XY:

0.739

AC XY:

54943

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.927

AC:

38550

AN:

41564

American (AMR)

AF:

0.687

AC:

10500

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.710

AC:

2463

AN:

3470

East Asian (EAS)

AF:

0.661

AC:

3412

AN:

5164

South Asian (SAS)

AF:

0.751

AC:

3622

AN:

4824

European-Finnish (FIN)

AF:

0.539

AC:

5687

AN:

10546

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.688

AC:

46797

AN:

67970

Other (OTH)

AF:

0.715

AC:

1507

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1384

2767

4151

5534

6918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.707

Hom.:

140687

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

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Protoporphyria, erythropoietic, 1

Benign:3

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.19

(source)

DANN

Benign

0.40

PhyloP100

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over