rs56767103

Variant names:

• chr22-36506212-G-A
• rs56767103
• NM_001102371.2:c.211C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R71H) has been classified as Uncertain significance.

• 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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102371.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXRED2	NM_001102371.2	MANE Select	c.211C>T	p.Arg71Cys	missense	Exon 2 of 9	NP_001095841.1	Q8IWF2-1
	FOXRED2	NM_001438722.1		c.211C>T	p.Arg71Cys	missense	Exon 1 of 8	NP_001425651.1
	FOXRED2	NM_024955.6		c.211C>T	p.Arg71Cys	missense	Exon 2 of 9	NP_079231.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXRED2	ENST00000397224.9	TSL:1 MANE Select	c.211C>T	p.Arg71Cys	missense	Exon 2 of 9	ENSP00000380401.4	Q8IWF2-1
	FOXRED2	ENST00000216187.10	TSL:1	c.211C>T	p.Arg71Cys	missense	Exon 2 of 9	ENSP00000216187.6	Q8IWF2-1
	FOXRED2	ENST00000397223.4	TSL:1	c.211C>T	p.Arg71Cys	missense	Exon 1 of 8	ENSP00000380400.4	Q8IWF2-1

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

GnomAD2 exomes AF: 0.00632 AC: 1581 AN: 250060 AF XY: 0.00455

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 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

African (AFR) AF: 0.0938 AC: 3141 AN: 33476

American (AMR) AF: 0.00295 AC: 132 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00360 AC: 94 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1111966

Other (OTH) AF: 0.00426 AC: 257 AN: 60392

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

African (AFR) AF: 0.0855 AC: 3555 AN: 41560

American (AMR) AF: 0.00607 AC: 93 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68030

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00974 Hom.: 108

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 v4.9

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
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.15
Sift	Benign	0.042	D
Sift4G	Uncertain	0.059	T
Polyphen		0.99	D
Vest4		0.54
MVP		0.55
MPC		1.9
ClinPred		0.042	T
GERP RS		5.0
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.79
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: rs56767103; hg19: chr22-36902259;