ENST00000400379.8:c.1021T>C

Variant names:

• chr21-44229931-A-G
• rs200250197
• ENST00000400379.8:c.1021T>C

Variant summary

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

The ENST00000400379.8(ICOSLG):​c.1021T>C​(p.Phe341Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F341I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 10)
• Consequence: ICOSLG ENST00000400379.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057094663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICOSLG	NM_015259.6	c.898+123T>C		intron_variant	Intron 6 of 6	ENST00000407780.8	NP_056074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICOSLG	ENST00000407780.8	c.898+123T>C		intron_variant	Intron 6 of 6	1	NM_015259.6	ENSP00000384432.3

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.70
DANN	Benign	0.20
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.00058	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.014
Sift	Uncertain	0.025	D
Sift4G	Benign	0.59	T
Vest4		0.060
MutPred		0.42		Gain of loop (P = 0.0079);
MVP		0.055
ClinPred		0.039	T
GERP RS		-2.5

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: rs200250197; hg19: chr21-45649814;