21-44230070-C-G

Variant names:

• chr21-44230070-C-G
• rs1362370615
• NM_015259.6:c.882G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_015259.6(ICOSLG):​c.882G>C​(p.Pro294Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 9)
• Consequence: ICOSLG NM_015259.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.88
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 21-44230070-C-G is Benign according to our data. Variant chr21-44230070-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2984562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.88 with no splicing effect.

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.882G>C	p.Pro294Pro	synonymous	Exon 6 of 7	NP_056074.1	O75144-1
	ICOSLG	NM_001283050.2		c.882G>C	p.Pro294Pro	synonymous	Exon 6 of 7	NP_001269979.1	O75144-2
	ICOSLG	NM_001395918.1		c.882G>C	p.Pro294Pro	synonymous	Exon 6 of 7	NP_001382847.1	A0A8V8TQV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICOSLG	ENST00000407780.8	TSL:1 MANE Select	c.882G>C	p.Pro294Pro	synonymous	Exon 6 of 7	ENSP00000384432.3	O75144-1
	ICOSLG	ENST00000400379.8	TSL:1	c.882G>C	p.Pro294Pro	synonymous	Exon 6 of 6	ENSP00000383230.3	K4DIA0
	ICOSLG	ENST00000344330.9	TSL:1	c.882G>C	p.Pro294Pro	synonymous	Exon 6 of 7	ENSP00000339477.4	O75144-2

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 7

GnomAD4 genome Cov.: 9

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.87
DANN	Benign	0.53
PhyloP100		-4.9
PromoterAI		-0.0067	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1362370615; hg19: chr21-45649953;