9-21227899-C-G

Variant names:

• chr9-21227899-C-G
• rs1818648215
• NM_021268.2:c.275G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021268.2(IFNA17):​c.275G>C​(p.Ser92Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: IFNA17 NM_021268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0470
• Publications: 0 publications found

Genes affected

IFNA17 (HGNC:5422): (interferon alpha 17) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; lymphocyte activation involved in immune response; and positive regulation of peptidyl-serine phosphorylation of STAT protein. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in Crimean-Congo hemorrhagic fever and sarcoidosis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055912018).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021268.2. 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
	IFNA17	NM_021268.2	MANE Select	c.275G>C	p.Ser92Thr	missense	Exon 1 of 1	NP_067091.1	P01571

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA17	ENST00000413767.2	TSL:6 MANE Select	c.275G>C	p.Ser92Thr	missense	Exon 1 of 1	ENSP00000411940.2	P01571

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461710 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727164

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111878

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000312 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.3
DANN	Benign	0.83
DEOGEN2	Benign	0.074	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.047
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.012
Sift	Benign	0.48	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.057
MutPred		0.36		Loss of disorder (P = 0.0825)
MVP		0.15
MPC		0.015
ClinPred		0.044	T
GERP RS		-2.2
PromoterAI		0.020	Neutral
Varity_R		0.074
gMVP		0.073
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1818648215; hg19: chr9-21227898;