1-78650220-T-C

Position:

• chr1-78650220-T-C

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI44	NM_006417.5	c.25T>C	p.Trp9Arg	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.25T>C	p.Trp9Arg	missense_variant	2/9	1	NM_006417.5	ENSP00000359783.4

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

GnomAD3 exomes AF: 0.0929 AC: 23316 AN: 250866 Hom.: 1161 AF XY: 0.0954 AC XY: 12930 AN XY: 135536

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 SAS exome AF: 0.137

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

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0975

Gnomad4 ASJ exome AF: 0.0717

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0592

Gnomad4 NFE exome AF: 0.0801

Gnomad4 OTH exome AF: 0.0940

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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0552

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0888 Hom.: 945

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 v4.3

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
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
Varity_R		0.19
gMVP		0.56

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

LitVar

Other links and lift over

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