rs10488764

Variant names:

• chr11-110460907-G-A
• rs10488764
• NM_004109.5:c.441-1447G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FDX1	NM_004109.5	c.441-1447G>A		intron_variant	Intron 3 of 3	ENST00000260270.3	NP_004100.1
FDX1	XM_047426566.1	c.264-1447G>A		intron_variant	Intron 3 of 3		XP_047282522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDX1	ENST00000260270.3	c.441-1447G>A		intron_variant	Intron 3 of 3	1	NM_004109.5	ENSP00000260270.2

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

African (AFR) AF: 0.205 AC: 8510 AN: 41480

American (AMR) AF: 0.181 AC: 2767 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3466

East Asian (EAS) AF: 0.265 AC: 1370 AN: 5162

South Asian (SAS) AF: 0.199 AC: 957 AN: 4814

European-Finnish (FIN) AF: 0.225 AC: 2382 AN: 10574

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10086 AN: 68014

Other (OTH) AF: 0.183 AC: 387 AN: 2112

Alfa AF: 0.159 Hom.: 8592

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
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10488764; hg19: chr11-110331631;