Genetic Variant ICOSLG:p.Pro294Pro (chr21-44230070-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_015259.6(ICOSLG):c.882G>A(p.Pro294Pro) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. P294P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000027 ( 1 hom., cov: 9)

Exomes 𝑓: 0.000020 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

ICOSLG
NM_015259.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.88

Publications

0 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 -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-4.88 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015259.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ICOSLG	NM_015259.6	MANE Select	c.882G>A	p.Pro294Pro	synonymous	Exon 6 of 7	NP_056074.1	O75144-1
ICOSLG	NM_001283050.2		c.882G>A	p.Pro294Pro	synonymous	Exon 6 of 7	NP_001269979.1	O75144-2
ICOSLG	NM_001395918.1		c.882G>A	p.Pro294Pro	synonymous	Exon 6 of 7	NP_001382847.1	A0A8V8TQV9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ICOSLG	ENST00000407780.8	TSL:1 MANE Select	c.882G>A	p.Pro294Pro	synonymous	Exon 6 of 7	ENSP00000384432.3	O75144-1
ICOSLG	ENST00000400379.8	TSL:1	c.882G>A	p.Pro294Pro	synonymous	Exon 6 of 6	ENSP00000383230.3	K4DIA0
ICOSLG	ENST00000344330.9	TSL:1	c.882G>A	p.Pro294Pro	synonymous	Exon 6 of 7	ENSP00000339477.4	O75144-2

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

74930

Hom.:

Cov.:

show subpopulations

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:

0.0000614

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000646

AC:

AN:

154848

AF XY:

0.0000122

show subpopulations

Gnomad AFR exome

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000200

AC:

AN:

698580

Hom.:

Cov.:

AF XY:

0.0000231

AC XY:

AN XY:

345948

show subpopulations

African (AFR)

AF:

0.0000509

AC:

AN:

19644

American (AMR)

AF:

0.00

AC:

AN:

16392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13310

East Asian (EAS)

AF:

0.00

AC:

AN:

23970

South Asian (SAS)

AF:

0.00

AC:

AN:

47078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3704

European-Non Finnish (NFE)

AF:

0.0000248

AC:

AN:

524618

Other (OTH)

AF:

0.00

AC:

AN:

31848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000267

AC:

AN:

74930

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

36316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21364

American (AMR)

AF:

0.00

AC:

AN:

7396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1936

East Asian (EAS)

AF:

0.00

AC:

AN:

3248

South Asian (SAS)

AF:

0.00

AC:

AN:

2590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.0000614

AC:

AN:

32598

Other (OTH)

AF:

0.00

AC:

AN:

1058

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000959

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.5

(source)

DANN

Benign

0.56

PhyloP100

-4.9

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over