1-18908593-G-C

Variant names:

• chr1-18908593-G-C
• rs566982605
• NM_001136265.2:c.1522C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136265.2(IFFO2):​c.1522C>G​(p.Arg508Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R508C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: IFFO2 NM_001136265.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

Genes affected

IFFO2 (HGNC:27006): (intermediate filament family orphan 2) Predicted to be located in intermediate filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3516354).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136265.2. 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
	IFFO2	NM_001136265.2	MANE Select	c.1522C>G	p.Arg508Gly	missense	Exon 9 of 9	NP_001129737.1	Q5TF58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFFO2	ENST00000455833.7	TSL:5 MANE Select	c.1522C>G	p.Arg508Gly	missense	Exon 9 of 9	ENSP00000387941.2	Q5TF58
	IFFO2	ENST00000944819.1		c.1585C>G	p.Arg529Gly	missense	Exon 10 of 10	ENSP00000614878.1
	IFFO2	ENST00000416166.1	TSL:3	c.745C>G	p.Arg249Gly	missense	Exon 8 of 8	ENSP00000394655.1	H0Y4W3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399340 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690180

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078876

Other (OTH) AF: 0.00 AC: 0 AN: 58020

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.094
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.034	D
Polyphen		0.25	B
Vest4		0.41
MutPred		0.28		Loss of stability (P = 0.0139)
MVP		0.96
MPC		1.5
ClinPred		0.76	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.27
Mutation Taster		=77/23	polymorphism

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: rs566982605; hg19: chr1-19235087;