Variant rs1041951 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000140.5(FECH):c.287G>A(p.Arg96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,612,052 control chromosomes in the GnomAD database, including 16,271 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1040 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15231 hom. )

Consequence

FECH
NM_000140.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.522

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036842525).

BP6

Variant 18-57573273-C-T is Benign according to our data. Variant chr18-57573273-C-T is described in ClinVar as [Benign]. Clinvar id is 327434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-57573273-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/11	ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/11	1	NM_000140.5		P22830-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16084

AN:

152106

Hom.:

1040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.0912

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0224

Gnomad FIN

AF:

0.0937

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.101

AC:

25374

AN:

251432

Hom.:

1746

AF XY:

0.100

AC XY:

13591

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0554

Gnomad AMR exome

AF:

0.0559

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0276

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.136

AC:

198147

AN:

1459828

Hom.:

15231

Cov.:

AF XY:

0.133

AC XY:

96522

AN XY:

726364

show subpopulations

Gnomad4 AFR exome

AF:

0.0526

Gnomad4 AMR exome

AF:

0.0603

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0284

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.106

AC:

16083

AN:

152224

Hom.:

1040

Cov.:

AF XY:

0.0999

AC XY:

7436

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0576

Gnomad4 AMR

AF:

0.0910

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.0937

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.136

Hom.:

3874

Bravo

AF:

0.102

TwinsUK

AF:

0.159

AC:

590

ALSPAC

AF:

0.153

AC:

590

ESP6500AA

AF:

0.0608

AC:

268

ESP6500EA

AF:

0.152

AC:

1311

ExAC

AF:

0.103

AC:

12496

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.151

EpiControl

AF:

0.140

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

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

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

D;.;.;D;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.95

D;D;D;.;.

MetaRNN

Benign

0.0037

T;T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.1

L;.;.;.;.

MutationTaster

Benign

0.028

P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

N;N;.;.;.

REVEL

Uncertain

0.31

Sift

Benign

0.27

T;T;.;.;.

Sift4G

Benign

0.44

T;T;.;.;T

Polyphen

0.12

B;B;.;.;.

Vest4

0.052

MPC

0.46

ClinPred

0.011

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

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