rs56767103

Positions:

• chr22-36506212-G-A
• chr22-36506212-G-T

Variant summary

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

The NM_001102371.2(FOXRED2):​c.211C>T​(p.Arg71Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00458 in 1,614,090 control chromosomes in the GnomAD database, including 316 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.024 (148 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (168 hom.)
• Consequence: FOXRED2 NM_001102371.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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 (MetaRNN=0.0038172305).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXRED2	NM_001102371.2	c.211C>T	p.Arg71Cys	missense_variant	2/9	ENST00000397224.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXRED2	ENST00000397224.9	c.211C>T	p.Arg71Cys	missense_variant	2/9	1	NM_001102371.2	P1

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3688 AN: 152224 Hom.: 148 Cov.: 33

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00608

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00632 AC: 1581 AN: 250060 Hom.: 73 AF XY: 0.00455 AC XY: 616 AN XY: 135404

Gnomad AFR exome AF: 0.0887

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00249

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00253 AC: 3700 AN: 1461748 Hom.: 168 Cov.: 32 AF XY: 0.00218 AC XY: 1583 AN XY: 727190

Gnomad4 AFR exome AF: 0.0938

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.00360

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000531

Gnomad4 OTH exome AF: 0.00426

GnomAD4 genome AF: 0.0242 AC: 3693 AN: 152342 Hom.: 148 Cov.: 33 AF XY: 0.0233 AC XY: 1736 AN XY: 74498

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.00607

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00448 Hom.: 43

Bravo AF: 0.0273

ESP6500AA AF: 0.0874 AC: 385

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00799 AC: 970

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;T;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	.;.;D;D
MetaRNN	Benign	0.0038	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M;M;M;.
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.15
Sift	Benign	0.042	D;D;D;D
Sift4G	Uncertain	0.059	T;T;T;.
Polyphen		0.99	D;D;D;.
Vest4		0.54
MVP		0.55
MPC		1.9
ClinPred		0.042	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.79

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: rs56767103; hg19: chr22-36902259;