rs1601928358

Variant names:

• chr21-44229062-G-A
• rs1601928358
• ENST00000400379.8:c.*468C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001395918.1(ICOSLG):​c.*468C>T variant causes a 3 prime UTR 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: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ICOSLG NM_001395918.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 21-44229062-G-A is Benign according to our data. Variant chr21-44229062-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3616711.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395918.1. 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.899-18C>T		intron	N/A	NP_056074.1	O75144-1
	ICOSLG	NM_001395918.1		c.*468C>T		3_prime_UTR	Exon 7 of 7	NP_001382847.1	A0A8V8TQV9
	ICOSLG	NM_001283050.2		c.898+992C>T		intron	N/A	NP_001269979.1	O75144-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICOSLG	ENST00000400379.8	TSL:1	c.*468C>T		3_prime_UTR	Exon 6 of 6	ENSP00000383230.3	K4DIA0
	ICOSLG	ENST00000407780.8	TSL:1 MANE Select	c.899-18C>T		intron	N/A	ENSP00000384432.3	O75144-1
	ICOSLG	ENST00000344330.9	TSL:1	c.898+992C>T		intron	N/A	ENSP00000339477.4	O75144-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 629616 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 314616

African (AFR) AF: 0.00 AC: 0 AN: 10186

American (AMR) AF: 0.00 AC: 0 AN: 16808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13162

East Asian (EAS) AF: 0.00 AC: 0 AN: 21182

South Asian (SAS) AF: 0.00 AC: 0 AN: 33602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3456

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 483352

Other (OTH) AF: 0.00 AC: 0 AN: 27972

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

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	9.8
DANN	Benign	0.70
PhyloP100		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1601928358; hg19: chr21-45648945;