18-57545820-C-CA

Position:

• chr18-57545820-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000140.5(FECH):​c.*4891_*4892insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,566 control chromosomes in the GnomAD database, including 1,958 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1958 hom., cov: 29)
• Consequence: FECH NM_000140.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 18-57545820-C-CA is Benign according to our data. Variant chr18-57545820-C-CA is described in ClinVar as [Benign]. Clinvar id is 327327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.*4891_*4892insT		3_prime_UTR_variant	11/11	ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.*4891_*4892insT		3_prime_UTR_variant	11/11	1	NM_000140.5
FECH	ENST00000652755.1	c.*4891_*4892insT		3_prime_UTR_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22917 AN: 151446 Hom.: 1958 Cov.: 29

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 22925 AN: 151566 Hom.: 1958 Cov.: 29 AF XY: 0.155 AC XY: 11443 AN XY: 74048

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.166

Bravo AF: 0.136

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146687823; hg19: chr18-55213052;