rs273259

chr1-78628133-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006820.4(IFI44L):c.218A>G(p.His73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,611,096 control chromosomes in the GnomAD database, including 104,737 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.36 (10633 hom., cov: 32)
  • Exomes 𝑓: 0.35 (94104 hom.)
• Consequence: IFI44L NM_006820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.78

Genes affected

IFI44L (HGNC:17817): (interferon induced protein 44 like) Predicted to enable GTP binding activity. Involved in defense response to virus. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.300964E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI44L	NM_006820.4	c.218A>G	p.His73Arg	missense_variant	2/9	ENST00000370751.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI44L	ENST00000370751.10	c.218A>G	p.His73Arg	missense_variant	2/9	1	NM_006820.4	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55274 AN: 151772 Hom.: 10623 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.384 AC: 95657 AN: 249252 Hom.: 20079 AF XY: 0.384 AC XY: 51728 AN XY: 134818

Gnomad AFR exome AF: 0.367

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.327

Gnomad EAS exome AF: 0.755

Gnomad SAS exome AF: 0.417

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.374

GnomAD4 exome AF: 0.349 AC: 509913 AN: 1459206 Hom.: 94104 Cov.: 33 AF XY: 0.351 AC XY: 254856 AN XY: 725938

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.785

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.325

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.364 AC: 55334 AN: 151890 Hom.: 10633 Cov.: 32 AF XY: 0.369 AC XY: 27387 AN XY: 74212

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.382

Alfa AF: 0.346 Hom.: 20278

Bravo AF: 0.360

TwinsUK AF: 0.330 AC: 1222

ALSPAC AF: 0.325 AC: 1254

ESP6500AA AF: 0.376 AC: 1658

ESP6500EA AF: 0.327 AC: 2812

ExAC AF: 0.381 AC: 46242

Asia WGS AF: 0.567 AC: 1970 AN: 3478

EpiCase AF: 0.337

EpiControl AF: 0.324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.0010
Dann	Benign	0.080
Eigen	Benign	-2.7
Eigen_PC	Benign	-2.8
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.19	T;T;T
MetaRNN	Benign	9.3e-7	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.33	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.79	T;T;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.0080
MPC		0.013
ClinPred		0.0022	T
GERP RS		-6.2
Varity_R		0.026
gMVP		0.11

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: rs273259; hg19: chr1-79093818;