rs7242288

chr18-57576073-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.195-2708G>A 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 152,082 control chromosomes in the GnomAD database, including 5,480 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 (5480 hom., cov: 32)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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=-0.88).
• 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.195-2708G>A		intron_variant		ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.195-2708G>A		intron_variant		1	NM_000140.5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38682 AN: 151964 Hom.: 5467 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0942

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.231

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: 38722 AN: 152082 Hom.: 5480 Cov.: 32 AF XY: 0.246 AC XY: 18258 AN XY: 74362

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0937

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.247

Alfa AF: 0.254 Hom.: 809

Bravo AF: 0.258

Asia WGS AF: 0.0720 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.5
Dann	Benign	0.70

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: rs7242288; hg19: chr18-55243305;