Genetic Variant FDXR:c.1002+17C>T (chr17-74864131-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024417.5(FDXR):c.1002+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,612,686 control chromosomes in the GnomAD database, including 448,150 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 0.74 ( 42069 hom., cov: 32)

Exomes 𝑓: 0.74 ( 406081 hom. )

Consequence

FDXR
NM_024417.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

Publications

10 publications found

Variant links:

Genes affected

FDXR (HGNC:3642): (ferredoxin reductase) This gene encodes a mitochondrial flavoprotein that initiates electron transport for cytochromes P450 receiving electrons from NADPH. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]

FDXR Gene-Disease associations (from GenCC):

auditory neuropathy-optic atrophy syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FDXR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024417.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FDXR	NM_024417.5	MANE Select	c.1002+17C>T	intron	N/A	NP_077728.3
FDXR	NM_001258012.4		c.1131+17C>T	intron	N/A	NP_001244941.2
FDXR	NM_001258013.4		c.1095+17C>T	intron	N/A	NP_001244942.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FDXR	ENST00000293195.10	TSL:1 MANE Select	c.1002+17C>T	intron	N/A	ENSP00000293195.5
FDXR	ENST00000581530.5	TSL:1	c.1020+17C>T	intron	N/A	ENSP00000462972.1
FDXR	ENST00000578473.5	TSL:1	n.1690+17C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112617

AN:

151968

Hom.:

42047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.793

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.726

Gnomad NFE

AF:

0.749

Gnomad OTH

AF:

0.733

GnomAD4 exome

AF:

0.744

AC:

1085956

AN:

1460598

Hom.:

406081

Cov.:

AF XY:

0.744

AC XY:

540433

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.741

AC:

24819

AN:

33478

American (AMR)

AF:

0.834

AC:

37280

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

16280

AN:

26132

East Asian (EAS)

AF:

0.510

AC:

20238

AN:

39696

South Asian (SAS)

AF:

0.769

AC:

66326

AN:

86256

European-Finnish (FIN)

AF:

0.758

AC:

39618

AN:

52240

Middle Eastern (MID)

AF:

0.689

AC:

3977

AN:

5768

European-Non Finnish (NFE)

AF:

0.749

AC:

833276

AN:

1111930

Other (OTH)

AF:

0.731

AC:

44142

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

17994

35987

53981

71974

89968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20240

40480

60720

80960

101200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.741

AC:

112686

AN:

152088

Hom.:

42069

Cov.:

AF XY:

0.742

AC XY:

55196

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.739

AC:

30665

AN:

41498

American (AMR)

AF:

0.794

AC:

12134

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2145

AN:

3468

East Asian (EAS)

AF:

0.506

AC:

2612

AN:

5158

South Asian (SAS)

AF:

0.766

AC:

3696

AN:

4822

European-Finnish (FIN)

AF:

0.753

AC:

7972

AN:

10594

Middle Eastern (MID)

AF:

0.719

AC:

210

AN:

292

European-Non Finnish (NFE)

AF:

0.749

AC:

50918

AN:

67946

Other (OTH)

AF:

0.730

AC:

1544

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1480

2959

4439

5918

7398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.720

Hom.:

9019

Bravo

AF:

0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

PhyloP100

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over