Variant 21-44229831-C-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 ENST00000400379.8(ICOSLG):c.1121G>A(p.Arg374Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 1,079,362 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 3 hom., cov: 11)

Exomes 𝑓: 0.000037 ( 10 hom. )

Consequence

ICOSLG
ENST00000400379.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.03

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=0.0036784112).

BP6

Variant 21-44229831-C-T is Benign according to our data. Variant chr21-44229831-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652737.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICOSLG	NM_015259.6 linkuse as main transcript	c.898+223G>A		intron_variant		ENST00000407780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICOSLG	ENST00000407780.8 linkuse as main transcript	c.898+223G>A		intron_variant		1	NM_015259.6	A2	O75144-1

Frequencies

GnomAD3 genomes

AF:

0.000110

AC:

AN:

81994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00101

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:

0.00

Gnomad OTH

AF:

0.000862

GnomAD3 exomes

AF:

0.00951

AC:

1414

AN:

148714

Hom.:

AF XY:

0.00897

AC XY:

717

AN XY:

79970

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.00403

Gnomad ASJ exome

AF:

0.00720

Gnomad EAS exome

AF:

0.0000925

Gnomad SAS exome

AF:

0.00337

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.0162

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0000371

AC:

AN:

997368

Hom.:

Cov.:

AF XY:

0.0000243

AC XY:

AN XY:

494812

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000666

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000240

Gnomad4 OTH exome

AF:

0.0000229

GnomAD4 genome

AF:

0.000110

AC:

AN:

81994

Hom.:

Cov.:

AF XY:

0.0000505

AC XY:

AN XY:

39620

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00101

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000862

Alfa

AF:

0.0126

Hom.:

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0189

AC:

ExAC

AF:

0.00723

AC:

185

Asia WGS

AF:

0.000289

AC:

AN:

3476

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

Apr 01, 2024

ICOSLG: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

Cadd

Benign

0.34

Dann

Benign

0.81

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-0.050

REVEL

Benign

0.013

Sift

Pathogenic

0.0

Vest4

0.12

MVP

0.085

ClinPred

0.0036

GERP RS

-2.7

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

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