2-203951659-A-G

Position:

• chr2-203951659-A-G

Variant summary

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

The NM_012092.4(ICOS):​c.59-3977A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,064 control chromosomes in the GnomAD database, including 8,012 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 0.32 (8012 hom., cov: 32)
• Consequence: ICOS NM_012092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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]

ICOS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICOS	NM_012092.4	c.59-3977A>G		intron_variant		ENST00000316386.11	NP_036224.1
ICOS	XM_047444022.1	c.62-3977A>G		intron_variant			XP_047299978.1
ICOS	XR_007073112.1	n.111-3977A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICOS	ENST00000316386.11	c.59-3977A>G		intron_variant		1	NM_012092.4	ENSP00000319476.6
ICOS	ENST00000435193.1	c.59-3977A>G		intron_variant		1		ENSP00000415951.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48179 AN: 151946 Hom.: 7997 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.317 AC: 48237 AN: 152064 Hom.: 8012 Cov.: 32 AF XY: 0.315 AC XY: 23416 AN XY: 74334

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.364

Alfa AF: 0.302 Hom.: 6854

Bravo AF: 0.331

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.55

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: rs4355090; hg19: chr2-204816382;