9-21141086-C-A

Variant names:

• chr9-21141086-C-A
• rs370556360
• NM_002177.3:c.485G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002177.3(IFNW1):​c.485G>T​(p.Cys162Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C162Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IFNW1 NM_002177.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• Publications: 0 publications found

Genes affected

IFNW1 (HGNC:5448): (interferon omega 1) The protein encoded by this gene is an interferon and possesses antiviral activity. The encoded protein binds to the interferon alpha/beta receptor but not to the interferon gamma receptor. This intronless gene has several pseudogenes spread throughout the genome. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.966

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002177.3. 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
	IFNW1	NM_002177.3	MANE Select	c.485G>T	p.Cys162Phe	missense	Exon 1 of 1	NP_002168.1	P05000

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNW1	ENST00000380229.4	TSL:6 MANE Select	c.485G>T	p.Cys162Phe	missense	Exon 1 of 1	ENSP00000369578.2	P05000

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0062	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		2.2
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-10	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.96		Gain of MoRF binding (P = 0.0724)
MVP		0.57
MPC		0.015
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.96
gMVP		0.15
Mutation Taster		=83/17	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: rs370556360; hg19: chr9-21141085;