rs11571314

Positions:

• chr2-203957119-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.501+354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,002 control chromosomes in the GnomAD database, including 7,151 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 0.29 (7151 hom., cov: 32)
• Consequence: ICOS NM_012092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICOS	NM_012092.4	c.501+354A>G		intron_variant		ENST00000316386.11
ICOS	XM_047444022.1	c.504+354A>G		intron_variant
ICOS	XR_007073112.1	n.553+354A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICOS	ENST00000316386.11	c.501+354A>G		intron_variant		1	NM_012092.4	P2
ICOS	ENST00000435193.1	c.501+354A>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44515 AN: 151886 Hom.: 7118 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.293 AC: 44603 AN: 152002 Hom.: 7151 Cov.: 32 AF XY: 0.293 AC XY: 21795 AN XY: 74334

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.296

Alfa AF: 0.248 Hom.: 1012

Bravo AF: 0.300

Asia WGS AF: 0.311 AC: 1082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.19
DANN	Benign	0.37

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: rs11571314; hg19: chr2-204821842;