chr21-44229058-T-A

Variant names:

• chr21-44229058-T-A
• rs142566111
• ENST00000400379.8:c.*472A>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.*472A>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)
• Consequence: ICOSLG NM_001395918.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.715
• 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=-0.87).
• BP6: Variant 21-44229058-T-A is Benign according to our data. Variant chr21-44229058-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1648061.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.899-14A>T		intron	N/A	NP_056074.1	O75144-1
	ICOSLG	NM_001395918.1		c.*472A>T		3_prime_UTR	Exon 7 of 7	NP_001382847.1	A0A8V8TQV9
	ICOSLG	NM_001283050.2		c.898+996A>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.*472A>T		3_prime_UTR	Exon 6 of 6	ENSP00000383230.3	K4DIA0
	ICOSLG	ENST00000407780.8	TSL:1 MANE Select	c.899-14A>T		intron	N/A	ENSP00000384432.3	O75144-1
	ICOSLG	ENST00000344330.9	TSL:1	c.898+996A>T		intron	N/A	ENSP00000339477.4	O75144-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000242 AC: 6 AN: 248090 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000391

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	-0.87
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		-0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs142566111; hg19: chr21-45648941;