rs4819388

Variant names:

• chr21-44227538-T-A
• rs4819388
• NM_015259.6:c.*1496A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44227538-T-A
• chr21-44227538-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015259.6(ICOSLG):​c.*1496A>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ICOSLG NM_015259.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 57 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICOSLG	NM_015259.6	c.*1496A>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000407780.8	NP_056074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000407780.8	c.*1496A>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_015259.6	ENSP00000384432.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 65328 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 3

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 65328 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 31742

African (AFR) AF: 0.00 AC: 0 AN: 13472

American (AMR) AF: 0.00 AC: 0 AN: 6904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1888

East Asian (EAS) AF: 0.00 AC: 0 AN: 3186

South Asian (SAS) AF: 0.00 AC: 0 AN: 1878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 194

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 32440

Other (OTH) AF: 0.00 AC: 0 AN: 972

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		-0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4819388; hg19: chr21-45647421;