rs4675379

Variant names:

• chr2-203961372-G-A
• rs4675379
• NM_012092.4:c.*1773G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-203961372-G-A
• chr2-203961372-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012092.4(ICOS):​c.*1773G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ICOS NM_012092.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 21 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012092.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICOS	NM_012092.4	MANE Select	c.*1773G>A		3_prime_UTR	Exon 5 of 5	NP_036224.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICOS	ENST00000316386.11	TSL:1 MANE Select	c.*1773G>A		3_prime_UTR	Exon 5 of 5	ENSP00000319476.6
	ICOS	ENST00000435193.1	TSL:1	c.*1781G>A		3_prime_UTR	Exon 4 of 4	ENSP00000415951.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 23070 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12112

African (AFR) AF: 0.00 AC: 0 AN: 502

American (AMR) AF: 0.00 AC: 0 AN: 498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 660

East Asian (EAS) AF: 0.00 AC: 0 AN: 2670

South Asian (SAS) AF: 0.00 AC: 0 AN: 222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 102

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14364

Other (OTH) AF: 0.00 AC: 0 AN: 1186

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 57

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.39
PhyloP100		-2.3

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: rs4675379; hg19: chr2-204826095;