rs4675377

chr2-203949953-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012092.4(ICOS):c.59-5683C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,114 control chromosomes in the GnomAD database, including 34,560 homozygotes. 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 0.64 (34560 hom., cov: 32)
• Consequence: ICOS NM_012092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

ICOS (HGNC:5351): (inducible T cell costimulator) The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses, and regulation of cell proliferation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICOS	NM_012092.4	c.59-5683C>T		intron_variant		ENST00000316386.11
ICOS	XM_047444022.1	c.62-5683C>T		intron_variant
ICOS	XR_007073112.1	n.111-5683C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICOS	ENST00000316386.11	c.59-5683C>T		intron_variant		1	NM_012092.4	P2
ICOS	ENST00000435193.1	c.59-5683C>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97746 AN: 151996 Hom.: 34556 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.643 AC: 97764 AN: 152114 Hom.: 34560 Cov.: 32 AF XY: 0.646 AC XY: 48073 AN XY: 74376

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.646

Alfa AF: 0.747 Hom.: 21560

Bravo AF: 0.621

Asia WGS AF: 0.731 AC: 2541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.092
Dann	Benign	0.54

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: rs4675377; hg19: chr2-204814676;