2-203956891-C-G

Position:

• chr2-203956891-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012092.4(ICOS):​c.501+126C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 696,374 control chromosomes in the GnomAD database, including 10,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1930 hom., cov: 32)
  • Exomes 𝑓: 0.16 (8177 hom.)
• Consequence: ICOS NM_012092.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-203956891-C-G is Benign according to our data. Variant chr2-203956891-C-G is described in ClinVar as [Benign]. Clinvar id is 1296788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICOS	NM_012092.4	c.501+126C>G		intron_variant		ENST00000316386.11	NP_036224.1
ICOS	XM_047444022.1	c.504+126C>G		intron_variant			XP_047299978.1
ICOS	XR_007073112.1	n.553+126C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICOS	ENST00000316386.11	c.501+126C>G		intron_variant		1	NM_012092.4	ENSP00000319476	P2
ICOS	ENST00000435193.1	c.501+126C>G		intron_variant		1		ENSP00000415951	A2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23618 AN: 151978 Hom.: 1922 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.164 AC: 89504 AN: 544278 Hom.: 8177 AF XY: 0.172 AC XY: 50162 AN XY: 292138

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.155 AC: 23638 AN: 152096 Hom.: 1930 Cov.: 32 AF XY: 0.158 AC XY: 11733 AN XY: 74344

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.169

Alfa AF: 0.136 Hom.: 156

Bravo AF: 0.156

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.33
DANN	Benign	0.81

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: rs4270326; hg19: chr2-204821614;