rs1553499319

Positions:

• chr2-203955763-C-G
• chr2-203955763-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_012092.4(ICOS):​c.186C>G​(p.Leu62=) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L62L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ICOS NM_012092.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.249

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-203955763-C-G is Benign according to our data. Variant chr2-203955763-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1536623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.249 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICOS	NM_012092.4	c.186C>G	p.Leu62=	synonymous_variant	2/5	ENST00000316386.11
ICOS	XM_047444022.1	c.189C>G	p.Leu63=	synonymous_variant	2/5
ICOS	XR_007073112.1	n.238C>G		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICOS	ENST00000316386.11	c.186C>G	p.Leu62=	synonymous_variant	2/5	1	NM_012092.4	P2
ICOS	ENST00000435193.1	c.186C>G	p.Leu62=	synonymous_variant	2/4	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency, common variable, 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.3
DANN	Benign	0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-204820486;