rs552432

Variant names:

• chr17-74864131-G-A
• rs552432
• NM_024417.5:c.1002+17C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-74864131-G-A
• chr17-74864131-G-C
• chr17-74864131-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDXR	NM_024417.5	c.1002+17C>T		intron_variant	Intron 9 of 11	ENST00000293195.10	NP_077728.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDXR	ENST00000293195.10	c.1002+17C>T		intron_variant	Intron 9 of 11	1	NM_024417.5	ENSP00000293195.5

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112617 AN: 151968 Hom.: 42047 Cov.: 32

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.: 56 AF XY: 0.744 AC XY: 540433 AN XY: 726568

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

GnomAD4 genome AF: 0.741 AC: 112686 AN: 152088 Hom.: 42069 Cov.: 32 AF XY: 0.742 AC XY: 55196 AN XY: 74358

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

Alfa AF: 0.720 Hom.: 9019

Bravo AF: 0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	16
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

Other links and lift over

dbSNP: rs552432; hg19: chr17-72860253;