rs7230486

Variant names:

• chr18-57564929-C-A
• rs7230486
• NM_000140.5:c.598+1518G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-57564929-C-A
• chr18-57564929-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000140.5(FECH):​c.598+1518G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,230 control chromosomes in the GnomAD database, including 1,482 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 (1482 hom., cov: 33)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• protoporphyria, erythropoietic, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae)
• autosomal erythropoietic protoporphyria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FECH	NM_000140.5	c.598+1518G>T		intron_variant	Intron 5 of 10	ENST00000262093.11	NP_000131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11	c.598+1518G>T		intron_variant	Intron 5 of 10	1	NM_000140.5	ENSP00000262093.6

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17306 AN: 152112 Hom.: 1474 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0991

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

GnomAD4 genome AF: 0.114 AC: 17353 AN: 152230 Hom.: 1482 Cov.: 33 AF XY: 0.114 AC XY: 8454 AN XY: 74434

African (AFR) AF: 0.240 AC: 9964 AN: 41510

American (AMR) AF: 0.0630 AC: 964 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0799 AC: 277 AN: 3468

East Asian (EAS) AF: 0.148 AC: 768 AN: 5174

South Asian (SAS) AF: 0.116 AC: 560 AN: 4824

European-Finnish (FIN) AF: 0.0659 AC: 699 AN: 10608

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3869 AN: 68034

Other (OTH) AF: 0.101 AC: 213 AN: 2110

Alfa AF: 0.104 Hom.: 165

Bravo AF: 0.117

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.35
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7230486; hg19: chr18-55232161;