chr21-44230041-AC-A

Variant names:

• chr21-44230040-CA-CA
• ENST00000400379.8:c.

Variant summary

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

The ENST00000400379.8(ICOSLG):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 9)
• Consequence: ICOSLG ENST00000400379.8 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• 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: ENST00000400379.8. 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.		intron	N/A	NP_056074.1	O75144-1
	ICOSLG	NM_001283050.2		c.		intron	N/A	NP_001269979.1	O75144-2
	ICOSLG	NM_001395918.1		c.		intron	N/A	NP_001382847.1	A0A8V8TQV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICOSLG	ENST00000400379.8	TSL:1	c.		exon_region	Exon 6 of 6	ENSP00000383230.3	K4DIA0
	ICOSLG	ENST00000407780.8	TSL:1 MANE Select	c.		intron	N/A	ENSP00000384432.3	O75144-1
	ICOSLG	ENST00000344330.9	TSL:1	c.		intron	N/A	ENSP00000339477.4	O75144-2

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 9

GnomAD4 genome Cov.: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

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: chr21-45649923;