Variant 21-44229832-G-A 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+222C>T 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 0.0013 ( 7 hom., cov: 11)

Exomes 𝑓: 0.00016 ( 17 hom. )

Failed GnomAD Quality Control

Consequence

ICOSLG
ENST00000407780.8 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.982

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 (BayesDel_addAF=-0.795876).

BP6

Variant 21-44229832-G-A is Benign according to our data. Variant chr21-44229832-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652738.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICOSLG	NM_015259.6 linkuse as main transcript	c.898+222C>T		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+222C>T		intron_variant		1	NM_015259.6	ENSP00000384432	A2	O75144-1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

103

AN:

81870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000380

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:

0.000161

AC:

AN:

149202

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

80214

show subpopulations

Gnomad AFR exome

AF:

0.00219

Gnomad AMR exome

AF:

0.000244

Gnomad ASJ exome

AF:

0.000120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000362

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000157

AC:

156

AN:

995808

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

494086

show subpopulations

Gnomad4 AFR exome

AF:

0.00384

Gnomad4 AMR exome

AF:

0.000541

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000298

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000147

Gnomad4 OTH exome

AF:

0.000458

GnomAD4 genome

AF:

0.00126

AC:

103

AN:

81938

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

AN XY:

39644

show subpopulations

Gnomad4 AFR

AF:

0.00418

Gnomad4 AMR

AF:

0.000379

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:

0.000853

Alfa

AF:

0.000713

Hom.:

ExAC

AF:

0.0000388

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 01, 2023

ICOSLG: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.9

DANN

Benign

0.90

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0043

MutationTaster

Benign

1.0

D;N;N;N

Vest4

0.12

GERP RS

-1.6

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