rs10488764

Positions:

• chr11-110460907-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004109.5(FDX1):​c.441-1447G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,120 control chromosomes in the GnomAD database, including 2,550 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 0.18 (2550 hom., cov: 32)
• Consequence: FDX1 NM_004109.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

Genes affected

FDX1 (HGNC:3638): (ferredoxin 1) This gene encodes a small iron-sulfur protein that transfers electrons from NADPH through ferredoxin reductase to mitochondrial cytochrome P450, involved in steroid, vitamin D, and bile acid metabolism. Pseudogenes of this functional gene are found on chromosomes 20 and 21. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDX1	NM_004109.5	c.441-1447G>A		intron_variant		ENST00000260270.3
FDX1	XM_047426566.1	c.264-1447G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDX1	ENST00000260270.3	c.441-1447G>A		intron_variant		1	NM_004109.5	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27249 AN: 152002 Hom.: 2538 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.175

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.179 AC: 27294 AN: 152120 Hom.: 2550 Cov.: 32 AF XY: 0.186 AC XY: 13824 AN XY: 74366

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.183

Alfa AF: 0.158 Hom.: 4036

Bravo AF: 0.177

Asia WGS AF: 0.268 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.011
DANN	Benign	0.15

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: rs10488764; hg19: chr11-110331631;