rs2269221

Positions:

• chr18-57568208-G-A

Variant summary

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

The NM_000140.5(FECH):​c.464-1627C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,138 control chromosomes in the GnomAD database, including 1,326 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 0.11 (1326 hom., cov: 33)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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]

FECH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5	c.464-1627C>T		intron_variant		ENST00000262093.11	NP_000131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11	c.464-1627C>T		intron_variant		1	NM_000140.5	ENSP00000262093.6

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16581 AN: 152020 Hom.: 1323 Cov.: 33

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.109 AC: 16607 AN: 152138 Hom.: 1326 Cov.: 33 AF XY: 0.113 AC XY: 8388 AN XY: 74362

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0811

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.135

Alfa AF: 0.101 Hom.: 550

Bravo AF: 0.121

Asia WGS AF: 0.212 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.81

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: rs2269221; hg19: chr18-55235440;