rs516035

Variant names:

• chr17-74866033-G-T
• rs516035
• NM_024417.5:c.507+98C>A

Variant summary

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

The NM_024417.5(FDXR):​c.507+98C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 1,019,088 control chromosomes in the GnomAD database, including 311,984 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 0.82 (51598 hom., cov: 31)
  • Exomes 𝑓: 0.77 (260386 hom.)
• Consequence: FDXR NM_024417.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 5 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDXR	NM_024417.5	c.507+98C>A		intron_variant	Intron 5 of 11	ENST00000293195.10	NP_077728.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDXR	ENST00000293195.10	c.507+98C>A		intron_variant	Intron 5 of 11	1	NM_024417.5	ENSP00000293195.5

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124313 AN: 151920 Hom.: 51540 Cov.: 31

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.772 AC: 669578 AN: 867050 Hom.: 260386 AF XY: 0.772 AC XY: 344507 AN XY: 446424

African (AFR) AF: 0.948 AC: 20938 AN: 22088

American (AMR) AF: 0.854 AC: 32972 AN: 38604

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 12279 AN: 18796

East Asian (EAS) AF: 0.586 AC: 21406 AN: 36522

South Asian (SAS) AF: 0.795 AC: 52015 AN: 65390

European-Finnish (FIN) AF: 0.802 AC: 37000 AN: 46142

Middle Eastern (MID) AF: 0.701 AC: 2164 AN: 3086

European-Non Finnish (NFE) AF: 0.771 AC: 459778 AN: 596194

Other (OTH) AF: 0.771 AC: 31026 AN: 40228

GnomAD4 genome AF: 0.818 AC: 124427 AN: 152038 Hom.: 51598 Cov.: 31 AF XY: 0.819 AC XY: 60855 AN XY: 74302

African (AFR) AF: 0.944 AC: 39131 AN: 41474

American (AMR) AF: 0.824 AC: 12605 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2247 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3054 AN: 5146

South Asian (SAS) AF: 0.798 AC: 3840 AN: 4810

European-Finnish (FIN) AF: 0.799 AC: 8456 AN: 10586

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52407 AN: 67948

Other (OTH) AF: 0.794 AC: 1672 AN: 2106

Alfa AF: 0.808 Hom.: 8186

Bravo AF: 0.822

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.36
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs516035; hg19: chr17-72862155;