rs1333973

Positions:

• chr1-78628396-T-A
• chr1-78628396-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006820.4(IFI44L):​c.478+3T>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,482,864 control chromosomes in the GnomAD database, including 95,164 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9790 hom., cov: 32)
  • Exomes 𝑓: 0.35 (85374 hom.)
• Consequence: IFI44L NM_006820.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00001621
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI44L	NM_006820.4	c.478+3T>A		splice_donor_region_variant, intron_variant		ENST00000370751.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI44L	ENST00000370751.10	c.478+3T>A		splice_donor_region_variant, intron_variant		1	NM_006820.4	P1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52724 AN: 151816 Hom.: 9781 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.371

GnomAD3 exomes AF: 0.381 AC: 77914 AN: 204398 Hom.: 16332 AF XY: 0.381 AC XY: 42489 AN XY: 111510

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.756

Gnomad SAS exome AF: 0.420

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.348 AC: 462716 AN: 1330932 Hom.: 85374 Cov.: 22 AF XY: 0.349 AC XY: 231604 AN XY: 663152

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.347 AC: 52778 AN: 151932 Hom.: 9790 Cov.: 32 AF XY: 0.354 AC XY: 26252 AN XY: 74254

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.374

Alfa AF: 0.335 Hom.: 1688

Bravo AF: 0.341

Asia WGS AF: 0.561 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0060
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

Publications

LitVar

Other links and lift over

dbSNP: rs1333973; hg19: chr1-79094081;