rs55972840

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012092.4(ICOS):c.150A>G(p.Gln50Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,613,738 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 123 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 100 hom. )

Consequence

ICOS
NM_012092.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0390

Publications

1 publications found

Variant links:

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)

ICOS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 2-203955727-A-G is Benign according to our data. Variant chr2-203955727-A-G is described in ClinVar as Benign. ClinVar VariationId is 333733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.039 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ICOS	NM_012092.4 link	c.150A>G	p.Gln50Gln	synonymous_variant	Exon 2 of 5	ENST00000316386.11	NP_036224.1
ICOS	XM_047444022.1 link	c.153A>G	p.Gln51Gln	synonymous_variant	Exon 2 of 5		XP_047299978.1
ICOS	XR_007073112.1 link	n.202A>G		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICOS	ENST00000316386.11 link	c.150A>G	p.Gln50Gln	synonymous_variant	Exon 2 of 5	1	NM_012092.4	ENSP00000319476.6
ICOS	ENST00000435193.1 link	c.150A>G	p.Gln50Gln	synonymous_variant	Exon 2 of 4	1		ENSP00000415951.1

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3131

AN:

152134

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0715

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00773

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0168

GnomAD2 exomes

AF:

0.00530

AC:

1330

AN:

251020

AF XY:

0.00379

show subpopulations

Gnomad AFR exome

AF:

0.0732

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00213

AC:

3119

AN:

1461486

Hom.:

100

Cov.:

AF XY:

0.00186

AC XY:

1350

AN XY:

727048

show subpopulations

African (AFR)

AF:

0.0774

AC:

2589

AN:

33454

American (AMR)

AF:

0.00389

AC:

174

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.000255

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000684

AC:

AN:

1111742

Other (OTH)

AF:

0.00416

AC:

251

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

174

347

521

694

868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0206

AC:

3142

AN:

152252

Hom.:

123

Cov.:

AF XY:

0.0200

AC XY:

1487

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0716

AC:

2974

AN:

41554

American (AMR)

AF:

0.00772

AC:

118

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67990

Other (OTH)

AF:

0.0166

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

150

300

450

600

750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00924

Hom.:

Bravo

AF:

0.0233

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency, common variable, 1

Benign:3

Sep 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.9

(source)

DANN

Benign

0.53

PhyloP100

0.039

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over