1-78627929-C-A

Variant names:

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

Variant summary

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

The NM_006820.4(IFI44L):​c.14C>A​(p.Thr5Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,546 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T5I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (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 2 ACMG points.

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

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>A	p.Thr5Lys	missense	Exon 2 of 9	NP_006811.2	Q53G44-1
	IFI44L	NM_001375646.1		c.14C>A	p.Thr5Lys	missense	Exon 3 of 10	NP_001362575.1	Q53G44-1
	IFI44L	NM_001375647.1		c.-296-1022C>A		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>A	p.Thr5Lys	missense	Exon 2 of 9	ENSP00000359787.4	Q53G44-1
	IFI44L	ENST00000459784.6	TSL:3	c.-296-1022C>A		intron	N/A	ENSP00000506096.1	B4E019
	IFI44L	ENST00000486882.5	TSL:1	n.2260C>A		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441546 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 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: 0.0000191 AC: 1 AN: 52264

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102650

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.0096
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.038	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.60		Loss of sheet (P = 0.0054)
MVP		0.35
MPC		0.093
ClinPred		0.97	D
GERP RS		3.1
PromoterAI		-0.014	Neutral
Varity_R		0.51
gMVP		0.39
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: -23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs375524121; hg19: chr1-79093614;