9-21077548-G-C

Variant names:

• chr9-21077548-G-C
• NM_002176.4:c.322C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002176.4(IFNB1):​c.322C>G​(p.Leu108Val) 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 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IFNB1 NM_002176.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNB1	NM_002176.4	c.322C>G	p.Leu108Val	missense_variant	Exon 1 of 1	ENST00000380232.4	NP_002167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNB1	ENST00000380232.4	c.322C>G	p.Leu108Val	missense_variant	Exon 1 of 1	6	NM_002176.4	ENSP00000369581.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461694 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.0
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.089
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.022	D
Polyphen		0.65	P
Vest4		0.32
MutPred		0.74		Loss of catalytic residue at L108 (P = 0.1282);
MVP		0.60
MPC		0.022
ClinPred		0.87	D
GERP RS		1.3
Varity_R		0.36
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-21077547;