chr17-74862587-G-A

Position:

• chr17-74862587-G-A

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.*230C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00667 in 539,884 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (82 hom., cov: 34)
  • Exomes 𝑓: 0.0023 (20 hom.)
• Consequence: FDXR NM_024417.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.95

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 (BayesDel_noAF=-0.96).
• BP6: Variant 17-74862587-G-A is Benign according to our data. Variant chr17-74862587-G-A is described in ClinVar as [Benign]. Clinvar id is 1183174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDXR	NM_024417.5	c.*230C>T		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.*230C>T		3_prime_UTR_variant	12/12	1	NM_024417.5	ENSP00000293195	P3

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2698 AN: 152226 Hom.: 82 Cov.: 34

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00232 AC: 899 AN: 387540 Hom.: 20 Cov.: 5 AF XY: 0.00197 AC XY: 395 AN XY: 200290

Gnomad4 AFR exome AF: 0.0563

Gnomad4 AMR exome AF: 0.00508

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000341

Gnomad4 FIN exome AF: 0.0000748

Gnomad4 NFE exome AF: 0.000203

Gnomad4 OTH exome AF: 0.00492

GnomAD4 genome AF: 0.0177 AC: 2701 AN: 152344 Hom.: 82 Cov.: 34 AF XY: 0.0176 AC XY: 1311 AN XY: 74504

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.00843

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.0121 Hom.: 8

Bravo AF: 0.0205

Asia WGS AF: 0.00202 AC: 7 AN: 3478

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

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.6
DANN	Benign	0.77
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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: rs34607406; hg19: chr17-72858709;