1-78627929-C-G

Variant names:

• chr1-78627929-C-G
• rs375524121
• NM_006820.4:c.14C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006820.4(IFI44L):​c.14C>G​(p.Thr5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,593,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T5I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IFI44L NM_006820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26094168).

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.14C>G	p.Thr5Arg	missense	Exon 2 of 9	NP_006811.2	Q53G44-1
	IFI44L	NM_001375646.1		c.14C>G	p.Thr5Arg	missense	Exon 3 of 10	NP_001362575.1	Q53G44-1
	IFI44L	NM_001375647.1		c.-296-1022C>G		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.14C>G	p.Thr5Arg	missense	Exon 2 of 9	ENSP00000359787.4	Q53G44-1
	IFI44L	ENST00000459784.6	TSL:3	c.-296-1022C>G		intron	N/A	ENSP00000506096.1	B4E019
	IFI44L	ENST00000486882.5	TSL:1	n.2260C>G		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151964 Hom.: 0 Cov.: 32

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: 6.94e-7 AC: 1 AN: 1441546 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 715920

African (AFR) AF: 0.00 AC: 0 AN: 32676

American (AMR) AF: 0.00 AC: 0 AN: 41908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25274

East Asian (EAS) AF: 0.00 AC: 0 AN: 39170

South Asian (SAS) AF: 0.00 AC: 0 AN: 82466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102650

Other (OTH) AF: 0.00 AC: 0 AN: 59470

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151964 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74204

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	0.19
Eigen_PC	Benign	0.032
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.57		Loss of sheet (P = 0.0084)
MVP		0.36
MPC		0.095
ClinPred		0.98	D
GERP RS		3.1
PromoterAI		-0.012	Neutral
Varity_R		0.55
gMVP		0.40
Mutation Taster		=92/8	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: rs375524121; hg19: chr1-79093614;