rs15927

Positions:

• chr21-44227763-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015259.6(ICOSLG):​c.*1271G>A 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 0.017 (7 hom., cov: 1)
  • Exomes 𝑓: 0.0059 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ICOSLG NM_015259.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICOSLG	NM_015259.6	c.*1271G>A		3_prime_UTR_variant	7/7	ENST00000407780.8	NP_056074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000407780.8	c.*1271G>A		3_prime_UTR_variant	7/7	1	NM_015259.6	ENSP00000384432.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 598 AN: 35822 Hom.: 7 Cov.: 1 FAILED QC

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00962

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.0409

Gnomad FIN AF: 0.00407

Gnomad MID AF: 0.0246

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0236

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00586 AC: 283 AN: 48318 Hom.: 0 Cov.: 2 AF XY: 0.00601 AC XY: 138 AN XY: 22970

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00500

Gnomad4 EAS exome AF: 0.00505

Gnomad4 SAS exome AF: 0.00808

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.00574

Gnomad4 OTH exome AF: 0.00522

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0166 AC: 596 AN: 35864 Hom.: 7 Cov.: 1 AF XY: 0.0165 AC XY: 279 AN XY: 16866

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.0166

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.0431

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.00407

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.242 Hom.: 4201

Asia WGS AF: 0.448 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs15927; hg19: chr21-45647646;