rs533952

Positions:

• chr18-57569110-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000262093.11(FECH):​c.463+2282A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,200 control chromosomes in the GnomAD database, including 43,943 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43943 hom., cov: 33)
• Consequence: FECH ENST00000262093.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5	c.463+2282A>C		intron_variant		ENST00000262093.11	NP_000131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11	c.463+2282A>C		intron_variant		1	NM_000140.5	ENSP00000262093

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114611 AN: 152082 Hom.: 43908 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.754 AC: 114704 AN: 152200 Hom.: 43943 Cov.: 33 AF XY: 0.749 AC XY: 55732 AN XY: 74390

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.722

Alfa AF: 0.718 Hom.: 35924

Bravo AF: 0.765

Asia WGS AF: 0.713 AC: 2479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.0
DANN	Benign	0.74

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: rs533952; hg19: chr18-55236342;