chr17-74866908-C-T

Variant names:

• chr17-74866908-C-T
• rs1688149
• NM_024417.5:c.178-32G>A

Variant summary

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

The NM_001258012.4(FDXR):​c.275G>A​(p.Gly92Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,606,128 control chromosomes in the GnomAD database, including 508,827 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (52780 hom., cov: 32)
  • Exomes 𝑓: 0.79 (456047 hom.)
• Consequence: FDXR NM_001258012.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.936

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=0.004830122).
• BP6: Variant 17-74866908-C-T is Benign according to our data. Variant chr17-74866908-C-T is described in ClinVar as [Benign]. Clinvar id is 769224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDXR	NM_024417.5	c.178-32G>A		intron_variant	Intron 2 of 11	ENST00000293195.10	NP_077728.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDXR	ENST00000293195.10	c.178-32G>A		intron_variant	Intron 2 of 11	1	NM_024417.5	ENSP00000293195.5

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125873 AN: 152036 Hom.: 52721 Cov.: 32

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.790 AC: 1148778 AN: 1453972 Hom.: 456047 Cov.: 57 AF XY: 0.789 AC XY: 570251 AN XY: 722568

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.859

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.804

Gnomad4 FIN exome AF: 0.817

Gnomad4 NFE exome AF: 0.792

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.828 AC: 125988 AN: 152156 Hom.: 52780 Cov.: 32 AF XY: 0.829 AC XY: 61640 AN XY: 74380

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.802

Alfa AF: 0.793 Hom.: 8748

Bravo AF: 0.831

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
LIST_S2	Benign	0.23	T;T
MetaRNN	Benign	0.0048	T;T
Sift4G	Benign	0.44	T;T
Vest4		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1688149; hg19: chr17-72863030;