rs690514

Positions:

• chr17-74866471-T-C
• chr17-74866471-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024417.5(FDXR):​c.368A>G​(p.Gln123Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,612,948 control chromosomes in the GnomAD database, including 512,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (52960 hom., cov: 34)
  • Exomes 𝑓: 0.79 (459483 hom.)
• Consequence: FDXR NM_024417.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005993098).
• BP6: Variant 17-74866471-T-C is Benign according to our data. Variant chr17-74866471-T-C is described in ClinVar as [Benign]. Clinvar id is 769225.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDXR	NM_024417.5	c.368A>G	p.Gln123Arg	missense_variant	4/12	ENST00000293195.10	NP_077728.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDXR	ENST00000293195.10	c.368A>G	p.Gln123Arg	missense_variant	4/12	1	NM_024417.5	ENSP00000293195	P3

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126106 AN: 152090 Hom.: 52899 Cov.: 34

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.807

GnomAD4 exome AF: 0.791 AC: 1155779 AN: 1460740 Hom.: 459483 Cov.: 72 AF XY: 0.790 AC XY: 574313 AN XY: 726640

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.862

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.806

Gnomad4 FIN exome AF: 0.818

Gnomad4 NFE exome AF: 0.793

Gnomad4 OTH exome AF: 0.785

GnomAD4 genome AF: 0.829 AC: 126223 AN: 152208 Hom.: 52960 Cov.: 34 AF XY: 0.830 AC XY: 61747 AN XY: 74400

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.807

Alfa AF: 0.798 Hom.: 29731

Bravo AF: 0.832

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_noAF	Uncertain	0.12
CADD	Benign	0.024
DEOGEN2	Benign	0.0028	.;.;.;T;.;T;T;T;.
LIST_S2	Benign	0.36	T;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0060	T;T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T
Vest4		0.091
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
gMVP		0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs690514; hg19: chr17-72862593;