18-57544911-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000140.5(FECH):c.*5801T>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 0.0076 in 152,376 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0076 (15 hom., cov: 33)
• Consequence: FECH NM_000140.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33

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=-0.82).
• BP6: Variant 18-57544911-A-C is Benign according to our data. Variant chr18-57544911-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 327315.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0076 (1158/152376) while in subpopulation AFR AF= 0.0265 (1102/41588). AF 95% confidence interval is 0.0252. There are 15 homozygotes in gnomad4. There are 532 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.*5801T>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.*5801T>G		3_prime_UTR_variant	11/11	1	NM_000140.5
FECH	ENST00000652755.1	c.*5801T>G		3_prime_UTR_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.00761 AC: 1159 AN: 152258 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00573

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

GnomAD4 genome AF: 0.00760 AC: 1158 AN: 152376 Hom.: 15 Cov.: 33 AF XY: 0.00714 AC XY: 532 AN XY: 74532

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00482 Hom.: 1

Bravo AF: 0.00884

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.7
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139119026; hg19: chr18-55212143;