Variant 14-94101849-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_206949.3(IFI27L1):c.97G>A(p.Ala33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000985 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

IFI27L1
NM_206949.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.348

Variant links:

Genes affected

IFI27L1 (HGNC:19754): (interferon alpha inducible protein 27 like 1) Involved in apoptotic process. Predicted to be integral component of membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

IFI27L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03862679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI27L1	NM_206949.3 linkuse as main transcript	c.97G>A	p.Ala33Thr	missense_variant	4/5	ENST00000555523.6
IFI27L1	NM_145249.3 linkuse as main transcript	c.97G>A	p.Ala33Thr	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI27L1	ENST00000555523.6 linkuse as main transcript	c.97G>A	p.Ala33Thr	missense_variant	4/5	2	NM_206949.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000199

AC:

AN:

251444

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000992

AC:

145

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.97G>A (p.A33T) alteration is located in exon 4 (coding exon 3) of the IFI27L1 gene. This alteration results from a G to A substitution at nucleotide position 97, causing the alanine (A) at amino acid position 33 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.071

T;T;.;.;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.015

M_CAP

Benign

0.017

MetaRNN

Benign

0.039

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.2

M;M;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D

REVEL

Benign

0.14

Sift

Benign

0.045

D;D;T;T;T;T

Sift4G

Uncertain

0.053

T;T;D;D;D;D

Polyphen

0.64

P;P;.;.;.;.

Vest4

0.15

MVP

0.040

MPC

0.21

ClinPred

0.076

GERP RS

-0.86

Varity_R

0.14

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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