Variant rs8339 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.*248C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 466,038 control chromosomes in the GnomAD database, including 11,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4835 hom., cov: 32)

Exomes 𝑓: 0.17 ( 6313 hom. )

Consequence

FECH
NM_000140.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.157

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 (BayesDel_noAF=-0.92).

BP6

Variant 18-57550464-G-A is Benign according to our data. Variant chr18-57550464-G-A is described in ClinVar as [Benign]. Clinvar id is 327419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5 link	c.*248C>T		3_prime_UTR_variant	11/11	ENST00000262093.11	NP_000131.2	P22830-1Q7KZA3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093 link	c.*248C>T		3_prime_UTR_variant	11/11	1	NM_000140.5	ENSP00000262093.6		P22830-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33238

AN:

151986

Hom.:

4825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.219

GnomAD4 exome

AF:

0.169

AC:

53073

AN:

313934

Hom.:

6313

Cov.:

AF XY:

0.170

AC XY:

28051

AN XY:

164694

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.467

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.219

AC:

33304

AN:

152104

Hom.:

4835

Cov.:

AF XY:

0.221

AC XY:

16426

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.373

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.143

Hom.:

1097

Bravo

AF:

0.240

Asia WGS

AF:

0.339

AC:

1178

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.92

CADD

Benign

0.087

DANN

Benign

0.34

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