21-44238447-C-T

Variant names:

• chr21-44238447-C-T
• rs1165558487
• NM_015259.6:c.55+1G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015259.6(ICOSLG):​c.55+1G>A variant causes a splice donor, intron change. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: ICOSLG NM_015259.6 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• combined immunodeficiency

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• immunodeficiency 119

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICOSLG	NM_015259.6	c.55+1G>A		splice_donor_variant, intron_variant	Intron 2 of 6	ENST00000407780.8	NP_056074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000407780.8	c.55+1G>A		splice_donor_variant, intron_variant	Intron 2 of 6	1	NM_015259.6	ENSP00000384432.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 247856 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0	.;.;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.46
LIST_S2	Benign	0.0	.;.;.;.
MetaRNN	Benign	0.0	.;.;.;.
MutationAssessor	Benign	0.0	.;.;.;.
PhyloP100		4.0
PROVEAN	Benign	0.0	.;.;.;.
Sift	Pathogenic	0.0	.;.;.;.
Sift4G	Pathogenic	0.0	.;.;.;.
Vest4		0.0
GERP RS		3.3
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.76
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.99		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1165558487; hg19: chr21-45658330; COSMIC: COSV100723852; COSMIC: COSV100723852;