1-78650220-T-C

Variant names:

• chr1-78650220-T-C
• rs2070123
• NM_006417.5:c.25T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006417.5(IFI44):​c.25T>C​(p.Trp9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 1,605,474 control chromosomes in the GnomAD database, including 6,866 homozygotes. 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: 𝑓 0.10 (864 hom., cov: 32)
  • Exomes 𝑓: 0.087 (6002 hom.)
• Consequence: IFI44 NM_006417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 24 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017084777).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

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.25T>C	p.Trp9Arg	missense	Exon 2 of 9	NP_006408.3
	IFI44	NR_135641.1		n.152T>C		non_coding_transcript_exon	Exon 2 of 8
	IFI44	NR_135640.1		n.117+315T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI44	ENST00000370747.9	TSL:1 MANE Select	c.25T>C	p.Trp9Arg	missense	Exon 2 of 9	ENSP00000359783.4	Q8TCB0-1
	IFI44	ENST00000879047.1		c.25T>C	p.Trp9Arg	missense	Exon 2 of 10	ENSP00000549106.1
	IFI44	ENST00000879049.1		c.25T>C	p.Trp9Arg	missense	Exon 2 of 10	ENSP00000549108.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15536 AN: 152050 Hom.: 858 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.0929 AC: 23316 AN: 250866 AF XY: 0.0954

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.0909

Gnomad ASJ exome AF: 0.0686

Gnomad EAS exome AF: 0.124

Gnomad FIN exome AF: 0.0593

Gnomad NFE exome AF: 0.0795

Gnomad OTH exome AF: 0.0919

GnomAD4 exome AF: 0.0869 AC: 126300 AN: 1453306 Hom.: 6002 Cov.: 32 AF XY: 0.0886 AC XY: 63909 AN XY: 720952

African (AFR) AF: 0.141 AC: 4710 AN: 33332

American (AMR) AF: 0.0975 AC: 4349 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 1868 AN: 26054

East Asian (EAS) AF: 0.140 AC: 5524 AN: 39400

South Asian (SAS) AF: 0.137 AC: 11786 AN: 85900

European-Finnish (FIN) AF: 0.0592 AC: 3159 AN: 53348

Middle Eastern (MID) AF: 0.127 AC: 726 AN: 5732

European-Non Finnish (NFE) AF: 0.0801 AC: 88532 AN: 1104898

Other (OTH) AF: 0.0940 AC: 5646 AN: 60036

GnomAD4 genome AF: 0.102 AC: 15558 AN: 152168 Hom.: 864 Cov.: 32 AF XY: 0.103 AC XY: 7631 AN XY: 74418

African (AFR) AF: 0.132 AC: 5485 AN: 41496

American (AMR) AF: 0.129 AC: 1969 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3468

East Asian (EAS) AF: 0.130 AC: 673 AN: 5174

South Asian (SAS) AF: 0.142 AC: 686 AN: 4822

European-Finnish (FIN) AF: 0.0552 AC: 586 AN: 10618

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5536 AN: 67998

Other (OTH) AF: 0.114 AC: 241 AN: 2116

Alfa AF: 0.0901 Hom.: 1853

Bravo AF: 0.106

TwinsUK AF: 0.0828 AC: 307

ALSPAC AF: 0.0789 AC: 304

ESP6500AA AF: 0.134 AC: 590

ESP6500EA AF: 0.0817 AC: 703

ExAC AF: 0.0934 AC: 11343

Asia WGS AF: 0.132 AC: 461 AN: 3476

EpiCase AF: 0.0907

EpiControl AF: 0.0867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.44
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.13
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-11	D
REVEL	Benign	0.065
Sift	Uncertain	0.012	D
Sift4G	Benign	0.62	T
Polyphen		0.93	P
Vest4		0.12
MutPred		0.16		Loss of catalytic residue at L7 (P = 0.0021)
MPC		0.035
ClinPred		0.072	T
GERP RS		-0.72
PromoterAI		0.024	Neutral
Varity_R		0.19
gMVP		0.56
Mutation Taster		=99/1	polymorphism (auto)

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: rs2070123; hg19: chr1-79115905; COSMIC: COSV100877270; COSMIC: COSV100877270;