chr21-44229635-G-T

Variant names:

• chr21-44229635-G-T
• ENST00000400379.8:c.1317C>A
• ICOSLG p.Ala439Ala

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The ENST00000400379.8(ICOSLG):​c.1317C>A​(p.Ala439Ala) 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. A439A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ICOSLG ENST00000400379.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.808 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000400379.8. 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.898+419C>A		intron	N/A	NP_056074.1	O75144-1
	ICOSLG	NM_001283050.2		c.898+419C>A		intron	N/A	NP_001269979.1	O75144-2
	ICOSLG	NM_001395918.1		c.899-89C>A		intron	N/A	NP_001382847.1	A0A8V8TQV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICOSLG	ENST00000400379.8	TSL:1	c.1317C>A	p.Ala439Ala	synonymous	Exon 6 of 6	ENSP00000383230.3	K4DIA0
	ICOSLG	ENST00000407780.8	TSL:1 MANE Select	c.898+419C>A		intron	N/A	ENSP00000384432.3	O75144-1
	ICOSLG	ENST00000344330.9	TSL:1	c.898+419C>A		intron	N/A	ENSP00000339477.4	O75144-2

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 688348 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 346174

African (AFR) AF: 0.00 AC: 0 AN: 19652

American (AMR) AF: 0.00 AC: 0 AN: 16430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14012

East Asian (EAS) AF: 0.00 AC: 0 AN: 29174

South Asian (SAS) AF: 0.00 AC: 0 AN: 45030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2796

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 506442

Other (OTH) AF: 0.00 AC: 0 AN: 32330

GnomAD4 genome Cov.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.48
PhyloP100		-0.81
PromoterAI		-0.0095	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-45649518;