ICOSLG p.His301His

Variant names:

• chr21-44229039-C-C
• NM_015259.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr21-44229040--
• chr21-44229040-G-A

Variant summary

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

The NM_015259.6(ICOSLG):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. 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 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015259.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICOSLG	NM_015259.6	MANE Select	c.		exon_region	Exon 7 of 7	NP_056074.1	O75144-1
	ICOSLG	NM_001395918.1		c.		exon_region	Exon 7 of 7	NP_001382847.1	A0A8V8TQV9
	ICOSLG	NM_001365759.2		c.		exon_region	Exon 7 of 7	NP_001352688.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICOSLG	ENST00000407780.8	TSL:1 MANE Select	c.		exon_region	Exon 7 of 7	ENSP00000384432.3	O75144-1
	ICOSLG	ENST00000400379.8	TSL:1	c.		exon_region	Exon 6 of 6	ENSP00000383230.3	K4DIA0
	ICOSLG	ENST00000400379.8	TSL:1	c.		3_prime_UTR	Exon 6 of 6	ENSP00000383230.3	K4DIA0

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-45648922;