chr18-57545826-A-C

Position:

• chr18-57545826-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000140.5(FECH):​c.*4886T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,012 control chromosomes in the GnomAD database, including 5,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5767 hom., cov: 32)
• Consequence: FECH NM_000140.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.178

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 18-57545826-A-C is Benign according to our data. Variant chr18-57545826-A-C is described in ClinVar as [Benign]. Clinvar id is 327328.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.*4886T>G		3_prime_UTR_variant	11/11	ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.*4886T>G		3_prime_UTR_variant	11/11	1	NM_000140.5
FECH	ENST00000652755.1	c.*4886T>G		3_prime_UTR_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40156 AN: 151894 Hom.: 5771 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.264 AC: 40153 AN: 152012 Hom.: 5767 Cov.: 32 AF XY: 0.255 AC XY: 18931 AN XY: 74306

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.00310

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.254

Alfa AF: 0.292 Hom.: 3701

Bravo AF: 0.266

Asia WGS AF: 0.0830 AC: 293 AN: 3478

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7238897; hg19: chr18-55213058;