14-94106403-A-T

Variant names:

• chr14-94106403-A-T
• rs10873447
• ENST00000614204.4:c.-145+485A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000614204.4(IFI27):​c.-145+485A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,088 control chromosomes in the GnomAD database, including 10,651 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 0.36 (10651 hom., cov: 33)
• Consequence: IFI27 ENST00000614204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI27	XM_047431346.1	c.2+493A>T		intron_variant	Intron 1 of 4		XP_047287302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI27	ENST00000614204.4	c.-145+485A>T		intron_variant	Intron 2 of 5	5		ENSP00000479250.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 54012 AN: 151970 Hom.: 10640 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 54065 AN: 152088 Hom.: 10651 Cov.: 33 AF XY: 0.359 AC XY: 26685 AN XY: 74334

African (AFR) AF: 0.510 AC: 21139 AN: 41488

American (AMR) AF: 0.272 AC: 4165 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1355 AN: 3466

East Asian (EAS) AF: 0.452 AC: 2343 AN: 5180

South Asian (SAS) AF: 0.452 AC: 2184 AN: 4828

European-Finnish (FIN) AF: 0.348 AC: 3666 AN: 10546

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18132 AN: 67976

Other (OTH) AF: 0.350 AC: 740 AN: 2112

Alfa AF: 0.168 Hom.: 324

Bravo AF: 0.351

Asia WGS AF: 0.455 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.81
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs10873447; hg19: chr14-94572749;