18-57545828-A-AG

Variant summary

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

The NM_000140.5(FECH):c.*4883_*4884insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 152,252 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0063 (15 hom., cov: 32)
• Consequence: FECH NM_000140.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.35

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 18-57545828-A-AG is Benign according to our data. Variant chr18-57545828-A-AG is described in ClinVar as [Likely_benign]. Clinvar id is 327329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.*4883_*4884insC		3_prime_UTR_variant	11/11	ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.*4883_*4884insC		3_prime_UTR_variant	11/11	1	NM_000140.5
FECH	ENST00000652755.1	c.*4883_*4884insC		3_prime_UTR_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.00622 AC: 947 AN: 152134 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00478

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

GnomAD4 genome AF: 0.00627 AC: 954 AN: 152252 Hom.: 15 Cov.: 32 AF XY: 0.00729 AC XY: 543 AN XY: 74450

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00904

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00410 Hom.: 3

Bravo AF: 0.00948

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Protoporphyria, erythropoietic, 1 Benign:1

Likely 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: rs201434287; hg19: chr18-55213060;