rs77163359

Variant names:

• chr1-78628271-C-A
• rs77163359
• NM_006820.4:c.356C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-78628271-C-A
• chr1-78628271-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006820.4(IFI44L):​c.356C>A​(p.Thr119Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: IFI44L NM_006820.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.42
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0461573).

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.356C>A	p.Thr119Lys	missense	Exon 2 of 9	NP_006811.2	Q53G44-1
	IFI44L	NM_001375646.1		c.356C>A	p.Thr119Lys	missense	Exon 3 of 10	NP_001362575.1	Q53G44-1
	IFI44L	NM_001375647.1		c.-296-680C>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.356C>A	p.Thr119Lys	missense	Exon 2 of 9	ENSP00000359787.4	Q53G44-1
	IFI44L	ENST00000459784.6	TSL:3	c.-296-680C>A		intron	N/A	ENSP00000506096.1	B4E019
	IFI44L	ENST00000486882.5	TSL:1	n.2602C>A		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151920 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248756 AF XY: 0.00

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151920 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74156

African (AFR) AF: 0.0000242 AC: 1 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0010
DANN	Benign	0.18
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.017
Sift	Benign	0.92	T
Sift4G	Benign	0.91	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.57		Gain of solvent accessibility (P = 0.0038)
MVP		0.040
MPC		0.013
ClinPred		0.019	T
GERP RS		-7.2
PromoterAI		-0.011	Neutral
Varity_R		0.034
gMVP		0.16
Mutation Taster		=99/1	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: rs77163359; hg19: chr1-79093956;