rs4820237

chr22-36498606-C-Achr22-36498606-C-Gchr22-36498606-C-T

Variant summary

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

The NM_001102371.2(FOXRED2):c.1217-450G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,062 control chromosomes in the GnomAD database, including 25,533 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 0.54 (25533 hom., cov: 32)
• Consequence: FOXRED2 NM_001102371.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

Genes affected

FOXRED2 (HGNC:26264): (FAD dependent oxidoreductase domain containing 2) Enables flavin adenine dinucleotide binding activity. Involved in ubiquitin-dependent ERAD pathway. Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXRED2	NM_001102371.2	c.1217-450G>T		intron_variant		ENST00000397224.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXRED2	ENST00000397224.9	c.1217-450G>T		intron_variant		1	NM_001102371.2	P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82323 AN: 151944 Hom.: 25530 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.542 AC: 82345 AN: 152062 Hom.: 25533 Cov.: 32 AF XY: 0.535 AC XY: 39785 AN XY: 74310

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.587

Alfa AF: 0.668 Hom.: 43150

Bravo AF: 0.536

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.26
Dann	Benign	0.55

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: rs4820237; hg19: chr22-36894653;