1-78628013-A-G

Variant names:

• chr1-78628013-A-G
• rs143352734
• NM_006820.4:c.98A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006820.4(IFI44L):​c.98A>G​(p.His33Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,130 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. H33P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: IFI44L NM_006820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI44L	NM_006820.4	c.98A>G	p.His33Arg	missense_variant	Exon 2 of 9	ENST00000370751.10	NP_006811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI44L	ENST00000370751.10	c.98A>G	p.His33Arg	missense_variant	Exon 2 of 9	1	NM_006820.4	ENSP00000359787.4
IFI44L	ENST00000459784.6	c.-296-938A>G		intron_variant	Intron 2 of 8	3		ENSP00000506096.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460994 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726800

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74314

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;T;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.0	.;M;.
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-7.9	D;D;D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.59
MutPred		0.70		Gain of MoRF binding (P = 0.0351);Gain of MoRF binding (P = 0.0351);.;
MVP		0.46
MPC		0.10
ClinPred		1.0	D
GERP RS		3.3
Varity_R		0.54
gMVP		0.57

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: rs143352734; hg19: chr1-79093698;