14-94105764-G-T

Variant summary

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

The ENST00000614204.4(IFI27):c.-298-1G>T variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,058 control chromosomes in the GnomAD database, including 13,897 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 0.40 (13895 hom., cov: 32)
  • Exomes 𝑓: 0.27 (2 hom.)
• Consequence: IFI27 ENST00000614204.4 splice_acceptor
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926

Genes affected

IFI27 (HGNC:5397): (interferon alpha inducible protein 27) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity; identical protein binding activity; and lamin binding activity. Involved in several processes, including cellular protein metabolic process; defense response to other organism; and extrinsic apoptotic signaling pathway. Acts upstream of or within negative regulation of transcription by RNA polymerase II and regulation of protein export from nucleus. Located in mitochondrial membrane and nuclear inner membrane. [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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI27	ENST00000614204.4	c.-298-1G>T		splice_acceptor_variant		5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60540 AN: 151914 Hom.: 13871 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.269 AC: 7 AN: 26 Hom.: 2 Cov.: 0 AF XY: 0.300 AC XY: 6 AN XY: 20

Gnomad4 AFR exome AF: 0.833

Gnomad4 NFE exome AF: 0.100

GnomAD4 genome AF: 0.399 AC: 60621 AN: 152032 Hom.: 13895 Cov.: 32 AF XY: 0.401 AC XY: 29843 AN XY: 74330

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.398

Alfa AF: 0.323 Hom.: 3825

Bravo AF: 0.399

Asia WGS AF: 0.479 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	5.8
Dann	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9323902; hg19: chr14-94572110;