rs1736439

Variant names:

• chr18-57562663-T-C
• rs1736439
• NM_000140.5:c.705+211A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-57562663-T-C
• chr18-57562663-T-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000140.5(FECH):​c.705+211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,028 control chromosomes in the GnomAD database, including 26,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.59 (26731 hom., cov: 33)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.358
• Publications: 4 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: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• autosomal erythropoietic protoporphyria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-57562663-T-C is Benign according to our data. Variant chr18-57562663-T-C is described in ClinVar as Benign. ClinVar VariationId is 1264025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000140.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FECH	NM_000140.5	MANE Select	c.705+211A>G		intron	N/A	NP_000131.2	P22830-1
	FECH	NM_001012515.4		c.723+211A>G		intron	N/A	NP_001012533.1	P22830-2
	FECH	NM_001374778.1		c.705+211A>G		intron	N/A	NP_001361707.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FECH	ENST00000262093.11	TSL:1 MANE Select	c.705+211A>G		intron	N/A	ENSP00000262093.6	P22830-1
	FECH	ENST00000652755.1		c.723+211A>G		intron	N/A	ENSP00000498358.1	P22830-2
	FECH	ENST00000878110.1		c.705+211A>G		intron	N/A	ENSP00000548169.1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89768 AN: 151910 Hom.: 26705 Cov.: 33

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.591 AC: 89856 AN: 152028 Hom.: 26731 Cov.: 33 AF XY: 0.587 AC XY: 43649 AN XY: 74300

African (AFR) AF: 0.562 AC: 23318 AN: 41456

American (AMR) AF: 0.603 AC: 9215 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2205 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3144 AN: 5174

South Asian (SAS) AF: 0.585 AC: 2819 AN: 4816

European-Finnish (FIN) AF: 0.488 AC: 5148 AN: 10550

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.622 AC: 42268 AN: 67968

Other (OTH) AF: 0.585 AC: 1234 AN: 2110

Alfa AF: 0.589 Hom.: 4155

Bravo AF: 0.595

Asia WGS AF: 0.596 AC: 2069 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.48
PhyloP100		-0.36
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: rs1736439; hg19: chr18-55229895;