NM_000140.5:c.706-1183G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000140.5(FECH):​c.706-1183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,280 control chromosomes in the GnomAD database, including 1,092 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.093 ( 1092 hom., cov: 33)

Consequence

FECH
NM_000140.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.12

Publications

3 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FECHNM_000140.5 linkc.706-1183G>A intron_variant Intron 6 of 10 ENST00000262093.11 NP_000131.2 P22830-1Q7KZA3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FECHENST00000262093.11 linkc.706-1183G>A intron_variant Intron 6 of 10 1 NM_000140.5 ENSP00000262093.6 P22830-1

Frequencies

GnomAD3 genomes
AF:
0.0929
AC:
14143
AN:
152162
Hom.:
1089
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0497
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.230
Gnomad ASJ
AF:
0.0591
Gnomad EAS
AF:
0.325
Gnomad SAS
AF:
0.100
Gnomad FIN
AF:
0.0633
Gnomad MID
AF:
0.0570
Gnomad NFE
AF:
0.0776
Gnomad OTH
AF:
0.109
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0930
AC:
14167
AN:
152280
Hom.:
1092
Cov.:
33
AF XY:
0.0973
AC XY:
7244
AN XY:
74454
show subpopulations
African (AFR)
AF:
0.0495
AC:
2059
AN:
41572
American (AMR)
AF:
0.231
AC:
3526
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.0591
AC:
205
AN:
3470
East Asian (EAS)
AF:
0.326
AC:
1685
AN:
5168
South Asian (SAS)
AF:
0.100
AC:
483
AN:
4830
European-Finnish (FIN)
AF:
0.0633
AC:
672
AN:
10612
Middle Eastern (MID)
AF:
0.0612
AC:
18
AN:
294
European-Non Finnish (NFE)
AF:
0.0776
AC:
5277
AN:
68024
Other (OTH)
AF:
0.113
AC:
239
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
617
1234
1850
2467
3084
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
158
316
474
632
790
<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:
0.0979
Hom.:
179
Bravo
AF:
0.107
Asia WGS
AF:
0.200
AC:
695
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.74
DANN
Benign
0.95
PhyloP100
-2.1
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12454808; hg19: chr18-55227658; API