dbSNP rs745321009: ICOSLG:p.Arg428Leu (chr21-44229669-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000400379.8(ICOSLG):c.1283G>T(p.Arg428Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R428H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 8)

Exomes 𝑓: 0.00017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ICOSLG
ENST00000400379.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.64

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04466504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICOSLG	NM_015259.6 link	c.898+385G>T		intron_variant	Intron 6 of 6	ENST00000407780.8	NP_056074.1	O75144-1A0N0L8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000407780.8 link	c.898+385G>T		intron_variant	Intron 6 of 6	1	NM_015259.6	ENSP00000384432.3		O75144-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

61450

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000362

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000647

AC:

AN:

139036

Hom.:

AF XY:

0.0000532

AC XY:

AN XY:

75246

show subpopulations

Gnomad AFR exome

AF:

0.000161

Gnomad AMR exome

AF:

0.000168

Gnomad ASJ exome

AF:

0.000374

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000174

AC:

145

AN:

831842

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

AN XY:

415088

show subpopulations

Gnomad4 AFR exome

AF:

0.00154

Gnomad4 AMR exome

AF:

0.000362

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000885

Gnomad4 OTH exome

AF:

0.000372

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000130

AC:

AN:

61514

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

AN XY:

29654

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000362

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000288

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.98

DANN

Benign

0.83

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.31

M_CAP

Benign

0.00053

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.95

PROVEAN

Benign

-0.43

REVEL

Benign

0.0020

Sift

Pathogenic

0.0

Sift4G

Benign

0.069

Vest4

0.041

MutPred

0.28

Loss of MoRF binding (P = 0.008);

MVP

0.085

ClinPred

0.023

GERP RS

-1.5

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over