chr18-57545084-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000140.5(FECH):​c.*5628C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,964 control chromosomes in the GnomAD database, including 10,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 10054 hom., cov: 32)

Consequence

FECH
NM_000140.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.80
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 18-57545084-G-T is Benign according to our data. Variant chr18-57545084-G-T is described in ClinVar as [Benign]. Clinvar id is 327316.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FECHNM_000140.5 linkuse as main transcriptc.*5628C>A 3_prime_UTR_variant 11/11 ENST00000262093.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FECHENST00000262093.11 linkuse as main transcriptc.*5628C>A 3_prime_UTR_variant 11/111 NM_000140.5 P22830-1
FECHENST00000652755.1 linkuse as main transcriptc.*5628C>A 3_prime_UTR_variant 11/11 P22830-2

Frequencies

GnomAD3 genomes
AF:
0.327
AC:
49684
AN:
151846
Hom.:
10055
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0955
Gnomad AMI
AF:
0.427
Gnomad AMR
AF:
0.311
Gnomad ASJ
AF:
0.420
Gnomad EAS
AF:
0.207
Gnomad SAS
AF:
0.239
Gnomad FIN
AF:
0.400
Gnomad MID
AF:
0.342
Gnomad NFE
AF:
0.469
Gnomad OTH
AF:
0.351
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.327
AC:
49674
AN:
151964
Hom.:
10054
Cov.:
32
AF XY:
0.319
AC XY:
23659
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.0953
Gnomad4 AMR
AF:
0.311
Gnomad4 ASJ
AF:
0.420
Gnomad4 EAS
AF:
0.206
Gnomad4 SAS
AF:
0.238
Gnomad4 FIN
AF:
0.400
Gnomad4 NFE
AF:
0.469
Gnomad4 OTH
AF:
0.353
Alfa
AF:
0.353
Hom.:
1984
Bravo
AF:
0.311
Asia WGS
AF:
0.230
AC:
803
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Protoporphyria, erythropoietic, 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.081
DANN
Benign
0.70

Splicing

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.

Other links and lift over

dbSNP: rs13732; hg19: chr18-55212316; API