chr14-94106403-A-T

Position:

• chr14-94106403-A-T

Variant summary

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

The XM_047431346.1(IFI27):​c.2+493A>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 XM_047431346.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-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/exons	MANE	Protein	UniProt
IFI27	XM_047431346.1	c.2+493A>T		intron_variant			XP_047287302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI27	ENST00000614204.4	c.-145+485A>T		intron_variant		5		ENSP00000479250

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

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.350

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10873447; hg19: chr14-94572749;