chr1-78628385-G-C

Variant names:

• chr1-78628385-G-C
• rs779556259
• NM_006820.4:c.470G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006820.4(IFI44L):​c.470G>C​(p.Arg157Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,388,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R157Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: IFI44L NM_006820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006820.4. 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
	IFI44L	NM_006820.4	MANE Select	c.470G>C	p.Arg157Pro	missense	Exon 2 of 9	NP_006811.2	Q53G44-1
	IFI44L	NM_001375646.1		c.470G>C	p.Arg157Pro	missense	Exon 3 of 10	NP_001362575.1	Q53G44-1
	IFI44L	NM_001375647.1		c.-296-566G>C		intron	N/A	NP_001362576.1	B4E019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI44L	ENST00000370751.10	TSL:1 MANE Select	c.470G>C	p.Arg157Pro	missense	Exon 2 of 9	ENSP00000359787.4	Q53G44-1
	IFI44L	ENST00000459784.6	TSL:3	c.-296-566G>C		intron	N/A	ENSP00000506096.1	B4E019
	IFI44L	ENST00000486882.5	TSL:1	n.2716G>C		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1388966 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 690132

African (AFR) AF: 0.00 AC: 0 AN: 30320

American (AMR) AF: 0.00 AC: 0 AN: 34394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23572

East Asian (EAS) AF: 0.00 AC: 0 AN: 39112

South Asian (SAS) AF: 0.00 AC: 0 AN: 77304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4662

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1070694

Other (OTH) AF: 0.0000174 AC: 1 AN: 57374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.0012	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0073	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.4
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.76		Loss of sheet (P = 0.0457)
MVP		0.27
MPC		0.10
ClinPred		0.99	D
GERP RS		2.3
PromoterAI		0.021	Neutral
Varity_R		0.83
gMVP		0.82
Mutation Taster		=89/11	polymorphism

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: rs779556259; hg19: chr1-79094070;