rs492274

Positions:

• chr18-57583662-T-C
• chr18-57583662-T-G

Variant summary

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

The NM_000140.5(FECH):​c.67+2892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,026 control chromosomes in the GnomAD database, including 15,744 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 0.45 (15744 hom., cov: 33)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FECH	NM_000140.5	c.67+2892A>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.67+2892A>G		intron_variant		1	NM_000140.5	ENSP00000262093

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67872 AN: 151908 Hom.: 15744 Cov.: 33

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.447 AC: 67899 AN: 152026 Hom.: 15744 Cov.: 33 AF XY: 0.445 AC XY: 33048 AN XY: 74296

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.469

Alfa AF: 0.488 Hom.: 21771

Bravo AF: 0.442

Asia WGS AF: 0.555 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.84

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: rs492274; hg19: chr18-55250894;