dbSNP rs7238897: FECH:c.*4886T>G (chr18-57545826-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000140.5(FECH):c.*4886T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,012 control chromosomes in the GnomAD database, including 5,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5767 hom., cov: 32)

Consequence

FECH
NM_000140.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.178

Publications

4 publications found

Variant links:

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, ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
autosomal erythropoietic protoporphyria
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FECH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 18-57545826-A-C is Benign according to our data. Variant chr18-57545826-A-C is described in ClinVar as Benign. ClinVar VariationId is 327328.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FECH	NM_000140.5	MANE Select	c.*4886T>G	3_prime_UTR	Exon 11 of 11	NP_000131.2	P22830-1
FECH	NM_001012515.4		c.*4886T>G	3_prime_UTR	Exon 11 of 11	NP_001012533.1	P22830-2
FECH	NM_001374778.1		c.*4886T>G	3_prime_UTR	Exon 10 of 10	NP_001361707.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FECH	ENST00000262093.11	TSL:1 MANE Select	c.*4886T>G		3_prime_UTR	Exon 11 of 11	ENSP00000262093.6	P22830-1
	FECH	ENST00000652755.1		c.*4886T>G		3_prime_UTR	Exon 11 of 11	ENSP00000498358.1	P22830-2

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40156

AN:

151894

Hom.:

5771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.257

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

GnomAD4 genome

AF:

0.264

AC:

40153

AN:

152012

Hom.:

5767

Cov.:

AF XY:

0.255

AC XY:

18931

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.284

AC:

11768

AN:

41470

American (AMR)

AF:

0.213

AC:

3258

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1222

AN:

3470

East Asian (EAS)

AF:

0.00310

AC:

AN:

5158

South Asian (SAS)

AF:

0.138

AC:

665

AN:

4820

European-Finnish (FIN)

AF:

0.195

AC:

2059

AN:

10574

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20281

AN:

67934

Other (OTH)

AF:

0.254

AC:

536

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1493

2986

4479

5972

7465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.284

Hom.:

5569

Bravo

AF:

0.266

Asia WGS

AF:

0.0830

AC:

293

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Protoporphyria, erythropoietic, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.36

PhyloP100

-0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over