1-78628396-T-G

Variant names:

• chr1-78628396-T-G
• rs1333973
• ENST00000486882.5:n.2727T>G

Variant summary

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

The ENST00000370751.10(IFI44L):​c.478+3T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,333,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: IFI44L ENST00000370751.10 splice_region, intron
• Scores: Splicing: ADA: 0.000008705
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684
• 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: 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 (BayesDel_noAF=-0.69).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370751.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI44L	NM_006820.4	MANE Select	c.478+3T>G		splice_region intron	N/A	NP_006811.2
	IFI44L	NM_001375646.1		c.478+3T>G		splice_region intron	N/A	NP_001362575.1
	IFI44L	NM_001375647.1		c.-296-555T>G		intron	N/A	NP_001362576.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI44L	ENST00000486882.5	TSL:1	n.2727T>G		non_coding_transcript_exon	Exon 1 of 7
	IFI44L	ENST00000370751.10	TSL:1 MANE Select	c.478+3T>G		splice_region intron	N/A	ENSP00000359787.4
	IFI44L	ENST00000459784.6	TSL:3	c.-296-555T>G		intron	N/A	ENSP00000506096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000225 AC: 3 AN: 1333594 Hom.: 0 Cov.: 22 AF XY: 0.00000452 AC XY: 3 AN XY: 664352

African (AFR) AF: 0.00 AC: 0 AN: 29082

American (AMR) AF: 0.00 AC: 0 AN: 33046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22588

East Asian (EAS) AF: 0.00 AC: 0 AN: 38816

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4184

European-Non Finnish (NFE) AF: 0.00000195 AC: 2 AN: 1024936

Other (OTH) AF: 0.00 AC: 0 AN: 55388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.49
PhyloP100		0.68
PromoterAI		-0.0069	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000087
dbscSNV1_RF	Benign	0.19
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: rs1333973; hg19: chr1-79094081;