1-78650577-A-G

Position:

• chr1-78650577-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006417.5(IFI44):​c.382A>G​(p.Lys128Glu) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFI44 NM_006417.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.55

Genes affected

IFI44 (HGNC:16938): (interferon induced protein 44) Predicted to be involved in immune response. Predicted to act upstream of or within response to bacterium. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IFI44 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037652493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI44	NM_006417.5	c.382A>G	p.Lys128Glu	missense_variant	2/9	ENST00000370747.9	NP_006408.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI44	ENST00000370747.9	c.382A>G	p.Lys128Glu	missense_variant	2/9	1	NM_006417.5	ENSP00000359783.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.382A>G (p.K128E) alteration is located in exon 2 (coding exon 1) of the IFI44 gene. This alteration results from a A to G substitution at nucleotide position 382, causing the lysine (K) at amino acid position 128 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.030
DANN	Benign	0.12
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.84	L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.27	N;N
REVEL	Benign	0.024
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0020	B;.
Vest4		0.035
MutPred		0.44		Loss of ubiquitination at K128 (P = 0.0233);.;
MVP		0.18
MPC		0.011
ClinPred		0.037	T
GERP RS		-6.2
Varity_R		0.055
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-79116262;