rs378299

Variant names:

• chr21-44241460-C-A
• rs378299
• ENST00000400377.4:c.-643G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44241460-C-A
• chr21-44241460-C-T

Variant summary

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

The ENST00000400377.4(ICOSLG):​c.-643G>T variant causes a upstream gene 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: not found (cov: 0)
• Consequence: ICOSLG ENST00000400377.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• Publications: 19 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

ENSG00000278158 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000400377.4	c.-643G>T		upstream_gene_variant		2		ENSP00000383228.3
ENSG00000278158	ENST00000619053.3	n.-91C>A		upstream_gene_variant		6
ICOSLG	ENST00000700354.1	n.-23G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		-0.93
PromoterAI		-0.28	Neutral

Splicing

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

Other links and lift over

dbSNP: rs378299; hg19: chr21-45661343;