14-94116589-C-G

Position:

• chr14-94116589-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The XM_047431346.1(IFI27):​c.462C>G​(p.Ser154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,340,828 control chromosomes in the GnomAD database, including 9,035 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 0.10 (1214 hom., cov: 32)
  • Exomes 𝑓: 0.082 (7821 hom.)
• Consequence: IFI27 XM_047431346.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.966 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI27	XM_047431346.1	c.462C>G	p.Ser154=	synonymous_variant	5/5
IFI27	NM_001130080.3	c.*62C>G		3_prime_UTR_variant	5/5	ENST00000621160.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI27	ENST00000621160.5	c.*62C>G		3_prime_UTR_variant	5/5	1	NM_001130080.3	P2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15734 AN: 152146 Hom.: 1211 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0817 AC: 97056 AN: 1188564 Hom.: 7821 Cov.: 16 AF XY: 0.0845 AC XY: 50621 AN XY: 598788

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.0753

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.0743

Gnomad4 NFE exome AF: 0.0506

Gnomad4 OTH exome AF: 0.0950

GnomAD4 genome AF: 0.103 AC: 15747 AN: 152264 Hom.: 1214 Cov.: 32 AF XY: 0.109 AC XY: 8149 AN XY: 74440

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0748

Gnomad4 NFE AF: 0.0516

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0221 Hom.: 13

Bravo AF: 0.113

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2799; hg19: chr14-94582926;