1-78650629-A-G

Variant names:

• chr1-78650629-A-G
• rs146103588
• NM_006417.5:c.434A>G

Variant summary

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

The NM_006417.5(IFI44):​c.434A>G​(p.Asp145Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D145V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IFI44 NM_006417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• Publications: 0 publications found

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]

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_006417.5. 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
	IFI44	NM_006417.5	MANE Select	c.434A>G	p.Asp145Gly	missense	Exon 2 of 9	NP_006408.3
	IFI44	NR_135641.1		n.561A>G		non_coding_transcript_exon	Exon 2 of 8
	IFI44	NR_135640.1		n.117+724A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI44	ENST00000370747.9	TSL:1 MANE Select	c.434A>G	p.Asp145Gly	missense	Exon 2 of 9	ENSP00000359783.4	Q8TCB0-1
	IFI44	ENST00000879047.1		c.434A>G	p.Asp145Gly	missense	Exon 2 of 10	ENSP00000549106.1
	IFI44	ENST00000879049.1		c.434A>G	p.Asp145Gly	missense	Exon 2 of 10	ENSP00000549108.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438692 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 714474

African (AFR) AF: 0.00 AC: 0 AN: 32150

American (AMR) AF: 0.00 AC: 0 AN: 40036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24702

East Asian (EAS) AF: 0.00 AC: 0 AN: 39504

South Asian (SAS) AF: 0.00 AC: 0 AN: 81932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52550

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5558

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103000

Other (OTH) AF: 0.00 AC: 0 AN: 59260

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.90	P
Vest4		0.28
MutPred		0.71		Gain of sheet (P = 0.0477)
MVP		0.58
MPC		0.027
ClinPred		0.96	D
GERP RS		3.3
Varity_R		0.44
gMVP		0.57
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs146103588; hg19: chr1-79116314;