chr17-74862678-G-T

Position:

• chr17-74862678-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024417.5(FDXR):​c.*139C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,196,774 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (242 hom., cov: 34)
  • Exomes 𝑓: 0.0081 (258 hom.)
• Consequence: FDXR NM_024417.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.884

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-74862678-G-T is Benign according to our data. Variant chr17-74862678-G-T is described in ClinVar as [Benign]. Clinvar id is 1242864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDXR	NM_024417.5	c.*139C>A		3_prime_UTR_variant	12/12	ENST00000293195.10	NP_077728.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDXR	ENST00000293195.10	c.*139C>A		3_prime_UTR_variant	12/12	1	NM_024417.5	ENSP00000293195	P3

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5179 AN: 152204 Hom.: 241 Cov.: 34

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.0830

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.00809 AC: 8449 AN: 1044452 Hom.: 258 Cov.: 14 AF XY: 0.00852 AC XY: 4397 AN XY: 516310

Gnomad4 AFR exome AF: 0.0987

Gnomad4 AMR exome AF: 0.00858

Gnomad4 ASJ exome AF: 0.0168

Gnomad4 EAS exome AF: 0.0604

Gnomad4 SAS exome AF: 0.0286

Gnomad4 FIN exome AF: 0.000126

Gnomad4 NFE exome AF: 0.00109

Gnomad4 OTH exome AF: 0.0188

GnomAD4 genome AF: 0.0341 AC: 5190 AN: 152322 Hom.: 242 Cov.: 34 AF XY: 0.0346 AC XY: 2577 AN XY: 74490

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.0826

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00172

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0163 Hom.: 17

Bravo AF: 0.0382

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs35033646; hg19: chr17-72858800;