9-21077717-G-T

Variant names:

• chr9-21077717-G-T
• rs1051922
• NM_002176.4:c.153C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002176.4(IFNB1):​c.153C>A​(p.Tyr51*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: IFNB1 NM_002176.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855
• Publications: 33 publications found

Genes affected

IFNB1 (HGNC:5434): (interferon beta 1) This gene encodes a cytokine that belongs to the interferon family of signaling proteins, which are released as part of the innate immune response to pathogens. The protein encoded by this gene belongs to the type I class of interferons, which are important for defense against viral infections. In addition, type I interferons are involved in cell differentiation and anti-tumor defenses. Following secretion in response to a pathogen, type I interferons bind a homologous receptor complex and induce transcription of genes such as those encoding inflammatory cytokines and chemokines. Overactivation of type I interferon secretion is linked to autoimmune diseases. Mice deficient for this gene display several phenotypes including defects in B cell maturation and increased susceptibility to viral infection. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002176.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNB1	NM_002176.4	MANE Select	c.153C>A	p.Tyr51*	stop_gained	Exon 1 of 1	NP_002167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNB1	ENST00000380232.4	TSL:6 MANE Select	c.153C>A	p.Tyr51*	stop_gained	Exon 1 of 1	ENSP00000369581.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 28862

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Pathogenic	26
DANN	Benign	0.93
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.012	N
PhyloP100		-0.85
Vest4		0.78
GERP RS		-8.8
PromoterAI		0.014	Neutral
Mutation Taster		=48/152	disease causing

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: rs1051922; hg19: chr9-21077716;