rs11571314

Variant names:

• chr2-203957119-A-G
• rs11571314
• NM_012092.4:c.501+354A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• common variable immunodeficiency

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• immunodeficiency, common variable, 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ICOS	NM_012092.4	c.501+354A>G		intron_variant	Intron 3 of 4	ENST00000316386.11	NP_036224.1
ICOS	XM_047444022.1	c.504+354A>G		intron_variant	Intron 3 of 4		XP_047299978.1
ICOS	XR_007073112.1	n.553+354A>G		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICOS	ENST00000316386.11	c.501+354A>G		intron_variant	Intron 3 of 4	1	NM_012092.4	ENSP00000319476.6
ICOS	ENST00000435193.1	c.501+354A>G		intron_variant	Intron 3 of 3	1		ENSP00000415951.1

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

African (AFR) AF: 0.414 AC: 17156 AN: 41428

American (AMR) AF: 0.291 AC: 4438 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1023 AN: 5182

South Asian (SAS) AF: 0.342 AC: 1651 AN: 4822

European-Finnish (FIN) AF: 0.227 AC: 2398 AN: 10582

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16239 AN: 67948

Other (OTH) AF: 0.296 AC: 620 AN: 2098

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11571314; hg19: chr2-204821842;