Variant rs2269219 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000140.5(FECH):c.68-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,613,044 control chromosomes in the GnomAD database, including 38,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.27 ( 6866 hom., cov: 32)

Exomes 𝑓: 0.19 ( 31549 hom. )

Consequence

FECH
NM_000140.5 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:6

Conservation

PhyloP100: 0.509

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 18-57580222-G-A is Benign according to our data. Variant chr18-57580222-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 550.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, Benign=4}. Variant chr18-57580222-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5 link	c.68-23C>T		intron_variant		ENST00000262093.11	NP_000131.2	P22830-1Q7KZA3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11 link	c.68-23C>T		intron_variant		1	NM_000140.5	ENSP00000262093.6		P22830-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41599

AN:

151926

Hom.:

6851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.260

GnomAD3 exomes

AF:

0.251

AC:

62889

AN:

250832

Hom.:

9458

AF XY:

0.240

AC XY:

32569

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.448

Gnomad AMR exome

AF:

0.416

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.311

Gnomad SAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.194

AC:

283768

AN:

1461000

Hom.:

31549

Cov.:

AF XY:

0.194

AC XY:

141175

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.225

Gnomad4 EAS exome

AF:

0.366

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.231

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.206

GnomAD4 genome

AF:

0.274

AC:

41673

AN:

152044

Hom.:

6866

Cov.:

AF XY:

0.278

AC XY:

20647

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.447

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.189

Hom.:

4713

Bravo

AF:

0.288

Asia WGS

AF:

0.294

AC:

1020

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Protoporphyria, erythropoietic, 1

Pathogenic:1Uncertain:1Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 1992	- -
Likely benign, criteria provided, single submitter	clinical testing	Centre for Mendelian Genomics, University Medical Centre Ljubljana	Jan 01, 2016	This variant was classified as: Likely benign. -
Uncertain significance, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University Hospital Muenster	Dec 08, 2021	ACMG categories: PS5,BS2,BP6,BP7 -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	This variant is associated with the following publications: (PMID: 8280787, 1729699, 27884173, 26789144) -

Jaundice;C0041834:Erythema

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 25, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.0

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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