rs12968109

Positions:

• chr18-57576579-G-A
• chr18-57576579-G-C
• chr18-57576579-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000140.5(FECH):​c.195-3214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,970 control chromosomes in the GnomAD database, including 5,475 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 0.25 (5475 hom., cov: 32)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.195-3214C>T		intron_variant		ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.195-3214C>T		intron_variant		1	NM_000140.5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38679 AN: 151852 Hom.: 5462 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0942

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.255 AC: 38719 AN: 151970 Hom.: 5475 Cov.: 32 AF XY: 0.246 AC XY: 18256 AN XY: 74284

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.246

Alfa AF: 0.202 Hom.: 779

Bravo AF: 0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.73

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: rs12968109; hg19: chr18-55243811;