18-57562663-T-C

Position:

• chr18-57562663-T-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.705+211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,028 control chromosomes in the GnomAD database, including 26,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.59 (26731 hom., cov: 33)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.358

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=-0.88).
• BP6: Variant 18-57562663-T-C is Benign according to our data. Variant chr18-57562663-T-C is described in ClinVar as [Benign]. Clinvar id is 1264025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5	c.705+211A>G		intron_variant		ENST00000262093.11	NP_000131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11	c.705+211A>G		intron_variant		1	NM_000140.5	ENSP00000262093

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89768 AN: 151910 Hom.: 26705 Cov.: 33

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.591 AC: 89856 AN: 152028 Hom.: 26731 Cov.: 33 AF XY: 0.587 AC XY: 43649 AN XY: 74300

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.585

Alfa AF: 0.590 Hom.: 4020

Bravo AF: 0.595

Asia WGS AF: 0.596 AC: 2069 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1736439; hg19: chr18-55229895;