rs8099511

Positions:

• chr18-57579636-T-C

Variant summary

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

The ENST00000262093.11(FECH):​c.194+437A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,964 control chromosomes in the GnomAD database, including 14,273 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 0.43 (14273 hom., cov: 31)
• Consequence: FECH ENST00000262093.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5	c.194+437A>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.194+437A>G		intron_variant		1	NM_000140.5	ENSP00000262093

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64599 AN: 151846 Hom.: 14251 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.425 AC: 64653 AN: 151964 Hom.: 14273 Cov.: 31 AF XY: 0.419 AC XY: 31095 AN XY: 74276

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.0337

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.417

Alfa AF: 0.446 Hom.: 22042

Bravo AF: 0.422

Asia WGS AF: 0.220 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.84
DANN	Benign	0.39

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: rs8099511; hg19: chr18-55246868;