chr22-36495811-C-A

Variant names:

• chr22-36495811-C-A
• rs5756219
• NM_001102371.2:c.1624+156G>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.1624+156G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,190 control chromosomes in the GnomAD database, including 14,541 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 0.39 (14541 hom., cov: 33)
• Consequence: FOXRED2 NM_001102371.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700
• Publications: 19 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]

LOC105373020 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.558 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.1624+156G>T		intron	N/A	NP_001095841.1	Q8IWF2-1
	FOXRED2	NM_001438722.1		c.1624+156G>T		intron	N/A	NP_001425651.1
	FOXRED2	NM_024955.6		c.1624+156G>T		intron	N/A	NP_079231.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXRED2	ENST00000397224.9	TSL:1 MANE Select	c.1624+156G>T		intron	N/A	ENSP00000380401.4	Q8IWF2-1
	FOXRED2	ENST00000216187.10	TSL:1	c.1624+156G>T		intron	N/A	ENSP00000216187.6	Q8IWF2-1
	FOXRED2	ENST00000397223.4	TSL:1	c.1624+156G>T		intron	N/A	ENSP00000380400.4	Q8IWF2-1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58821 AN: 152072 Hom.: 14539 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.0862

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.387 AC: 58823 AN: 152190 Hom.: 14541 Cov.: 33 AF XY: 0.379 AC XY: 28192 AN XY: 74406

African (AFR) AF: 0.104 AC: 4338 AN: 41550

American (AMR) AF: 0.568 AC: 8681 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1591 AN: 3472

East Asian (EAS) AF: 0.0862 AC: 447 AN: 5186

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4824

European-Finnish (FIN) AF: 0.395 AC: 4178 AN: 10576

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36962 AN: 67984

Other (OTH) AF: 0.437 AC: 922 AN: 2112

Alfa AF: 0.501 Hom.: 33685

Bravo AF: 0.393

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.5
DANN	Benign	0.69
PhyloP100		0.70
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: rs5756219; hg19: chr22-36891858; COSMIC: COSV53400241;