rs8094527

chr18-57570696-C-T

Variant summary

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

The NM_000140.5(FECH):c.463+696G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,064 control chromosomes in the GnomAD database, including 4,961 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 0.24 (4961 hom., cov: 32)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.463+696G>A		intron_variant		ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.463+696G>A		intron_variant		1	NM_000140.5

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37107 AN: 151946 Hom.: 4947 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0862

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.244 AC: 37147 AN: 152064 Hom.: 4961 Cov.: 32 AF XY: 0.235 AC XY: 17458 AN XY: 74322

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0861

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.231

Alfa AF: 0.249 Hom.: 811

Bravo AF: 0.247

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.10
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: rs8094527; hg19: chr18-55237928;