dbSNP rs15927: ICOSLG:c.*1271G>A (chr21-44227763-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.495

Publications

12 publications found

Variant links:

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

ICOSLG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.*1271G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000407780.8	NP_056074.1	O75144-1A0N0L8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000407780.8 link	c.*1271G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_015259.6	ENSP00000384432.3		O75144-1

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

598

AN:

35822

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00601

AC XY:

138

AN XY:

22970

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0183

AC:

AN:

438

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00500

AC:

AN:

400

East Asian (EAS)

AF:

0.00505

AC:

AN:

396

South Asian (SAS)

AF:

0.00808

AC:

AN:

866

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

178

European-Non Finnish (NFE)

AF:

0.00574

AC:

254

AN:

44262

Other (OTH)

AF:

0.00522

AC:

AN:

1724

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.248

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0166

AC:

596

AN:

35864

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

279

AN XY:

16866

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0260

AC:

160

AN:

6158

American (AMR)

AF:

0.0166

AC:

AN:

3844

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

1196

East Asian (EAS)

AF:

0.0431

AC:

AN:

1600

South Asian (SAS)

AF:

0.0395

AC:

AN:

836

European-Finnish (FIN)

AF:

0.00407

AC:

AN:

2210

Middle Eastern (MID)

AF:

0.0278

AC:

AN:

108

European-Non Finnish (NFE)

AF:

0.0116

AC:

224

AN:

19240

Other (OTH)

AF:

0.0237

AC:

AN:

464

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.272

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.255

Hom.:

7319

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

(source)

DANN

Benign

0.59

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs15927

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over