21-44230068-T-C

Position:

• chr21-44230068-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015259.6(ICOSLG):​c.884A>G​(p.Glu295Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 9)
  • Exomes 𝑓: 0.000016 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: ICOSLG NM_015259.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12327579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICOSLG	NM_015259.6	c.884A>G	p.Glu295Gly	missense_variant	6/7	ENST00000407780.8	NP_056074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000407780.8	c.884A>G	p.Glu295Gly	missense_variant	6/7	1	NM_015259.6	ENSP00000384432.3

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000157 AC: 11 AN: 700126 Hom.: 4 Cov.: 7 AF XY: 0.0000202 AC XY: 7 AN XY: 346760

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000209

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T;.;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.61	T;T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Benign	0.048
Sift	Benign	0.085	T;D;D;D
Sift4G	Uncertain	0.058	T;T;D;T
Polyphen		0.98	.;D;.;.
Vest4		0.18
MutPred		0.15		Loss of catalytic residue at E295 (P = 0.0696);Loss of catalytic residue at E295 (P = 0.0696);Loss of catalytic residue at E295 (P = 0.0696);.;
MVP		0.29
MPC		1.3
ClinPred		0.44	T
GERP RS		1.6
Varity_R		0.14
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

Other links and lift over

dbSNP: rs1161445658; hg19: chr21-45649951;