Variant 21-44229931-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000407780.8(ICOSLG):c.898+123T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 60 hom., cov: 10)

Exomes 𝑓: 0.0026 ( 755 hom. )

Failed GnomAD Quality Control

Consequence

ICOSLG
ENST00000407780.8 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.56

Variant links:

Genes affected

ICOSLG (HGNC:17087): (inducible T cell costimulator ligand) Enables identical protein binding activity. Predicted to be involved in T cell receptor signaling pathway and positive regulation of interleukin-4 production. Located in cytoplasmic ribonucleoprotein granule and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ICOSLG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043032765).

BP6

Variant 21-44229931-A-T is Benign according to our data. Variant chr21-44229931-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1879545.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICOSLG	NM_015259.6 linkuse as main transcript	c.898+123T>A		intron_variant		ENST00000407780.8	NP_056074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000407780.8 linkuse as main transcript	c.898+123T>A		intron_variant		1	NM_015259.6	ENSP00000384432	A2	O75144-1

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

157

AN:

77076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00143

Gnomad ASJ

AF:

0.00868

Gnomad EAS

AF:

0.000305

Gnomad SAS

AF:

0.00230

Gnomad FIN

AF:

0.000931

Gnomad MID

AF:

0.00446

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.00185

GnomAD3 exomes

AF:

0.00107

AC:

167

AN:

156024

Hom.:

AF XY:

0.00127

AC XY:

105

AN XY:

82798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.000238

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00257

AC:

1904

AN:

740462

Hom.:

755

Cov.:

AF XY:

0.00288

AC XY:

1063

AN XY:

368880

show subpopulations

Gnomad4 AFR exome

AF:

0.0000960

Gnomad4 AMR exome

AF:

0.000533

Gnomad4 ASJ exome

AF:

0.00679

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00524

Gnomad4 FIN exome

AF:

0.000679

Gnomad4 NFE exome

AF:

0.00251

Gnomad4 OTH exome

AF:

0.00289

GnomAD4 genome

AF:

0.00204

AC:

157

AN:

77144

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

AN XY:

37450

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00142

Gnomad4 ASJ

AF:

0.00868

Gnomad4 EAS

AF:

0.000306

Gnomad4 SAS

AF:

0.00231

Gnomad4 FIN

AF:

0.000931

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.00183

Alfa

AF:

0.00110

Hom.:

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000899

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ICOSLG: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.0

DANN

Benign

0.84

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.23

M_CAP

Benign

0.00048

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

0.22

REVEL

Benign

0.015

Sift

Uncertain

0.011

Sift4G

Benign

0.29

Vest4

0.16

MVP

0.055

ClinPred

0.0091

GERP RS

-2.5

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