rs11660001

chr18-57552997-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.1077+1263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,068 control chromosomes in the GnomAD database, including 2,773 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 0.18 (2773 hom., cov: 32)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.1077+1263C>T		intron_variant		ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.1077+1263C>T		intron_variant		1	NM_000140.5

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27916 AN: 151950 Hom.: 2771 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.184 AC: 27919 AN: 152068 Hom.: 2773 Cov.: 32 AF XY: 0.183 AC XY: 13591 AN XY: 74342

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.176

Alfa AF: 0.210 Hom.: 2049

Bravo AF: 0.177

Asia WGS AF: 0.183 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.0
Dann	Benign	0.49

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: rs11660001; hg19: chr18-55220229;