Variant 14-94115843-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000621160.5(IFI27):c.184G>A(p.Ala62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000868 in 1,601,742 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 1 hom. )

Consequence

IFI27
ENST00000621160.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0270

Variant links:

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]

IFI27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022180736).

BP6

Variant 14-94115843-G-A is Benign according to our data. Variant chr14-94115843-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2411105.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI27	NM_001130080.3 linkuse as main transcript	c.184G>A	p.Ala62Thr	missense_variant	4/5	ENST00000621160.5	NP_001123552.1
IFI27	XM_047431346.1 linkuse as main transcript	c.215G>A	p.Arg72His	missense_variant	4/5		XP_047287302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI27	ENST00000621160.5 linkuse as main transcript	c.184G>A	p.Ala62Thr	missense_variant	4/5	1	NM_001130080.3	ENSP00000483498	P2	P40305-2

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000303

AC:

AN:

224220

Hom.:

AF XY:

0.000281

AC XY:

AN XY:

121176

show subpopulations

Gnomad AFR exome

AF:

0.000149

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000666

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000902

AC:

1308

AN:

1449466

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

599

AN XY:

719874

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.000251

GnomAD4 genome

AF:

0.000545

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000765

Hom.:

Bravo

AF:

0.000529

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000322

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.27

DANN

Benign

0.43

DEOGEN2

Benign

0.0095

T;.;.;.;.;.;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.43

T;T;T;T;.;T;.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.022

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.34

Sift4G

Benign

0.84

T;T;T;T;T;T;T;T

Vest4

0.23, 0.27, 0.25, 0.23

MVP

0.12

ClinPred

0.0095

GERP RS

-3.4

Varity_R

0.017

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over