Variant 14-94100772-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PVS1_StrongPP5BS2

The NM_206949.3(IFI27L1):c.61+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,613,638 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely risk allele (no stars).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 11 hom. )

Consequence

IFI27L1
NM_206949.3 splice_donor

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely risk allele no assertion criteria provided P:1

Conservation

PhyloP100: 1.00

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 Uncertain_significance. Variant got 1 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.1015873 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP5

Variant 14-94100772-G-A is Pathogenic according to our data. Variant chr14-94100772-G-A is described in ClinVar as [Likely_risk_allele]. Clinvar id is 2428766.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI27L1	NM_206949.3 linkuse as main transcript	c.61+1G>A		splice_donor_variant		ENST00000555523.6
IFI27L1	NM_145249.3 linkuse as main transcript	c.61+1G>A		splice_donor_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI27L1	ENST00000555523.6 linkuse as main transcript	c.61+1G>A		splice_donor_variant		2	NM_206949.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000842

AC:

128

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00159

AC:

398

AN:

250540

Hom.:

AF XY:

0.00211

AC XY:

286

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00752

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000846

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00103

AC:

1498

AN:

1461412

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

916

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00691

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000555

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.000854

AC:

130

AN:

152226

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.000672

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00152

AC:

184

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00154

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Susceptibility to severe COVID-19

Pathogenic:1

Likely risk allele, no assertion criteria provided

research

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Jul 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.49

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

GERP RS

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.91

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.91

Position offset: -1

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