dbSNP rs1799969: ICAM1:p.Gly241Arg (chr19-10284116-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000201.3(ICAM1):c.721G>A(p.Gly241Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,914 control chromosomes in the GnomAD database, including 10,768 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.091 ( 943 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9825 hom. )

Consequence

ICAM1
NM_000201.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.71

Publications

217 publications found

Variant links:

Genes affected

ICAM1 (HGNC:5344): (intercellular adhesion molecule 1) This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by Rhinovirus as a receptor. [provided by RefSeq, Jul 2008]

ICAM1 links:

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

LIMASI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.133352E-4).

BP6

Variant 19-10284116-G-A is Benign according to our data. Variant chr19-10284116-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060438.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3 link	c.721G>A	p.Gly241Arg	missense_variant	Exon 4 of 7	ENST00000264832.8	NP_000192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8 link	c.721G>A	p.Gly241Arg	missense_variant	Exon 4 of 7	1	NM_000201.3	ENSP00000264832.2

Frequencies

GnomAD3 genomes

AF:

0.0911

AC:

13842

AN:

152000

Hom.:

942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0208

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.0724

GnomAD2 exomes

AF:

0.107

AC:

26844

AN:

251270

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.0270

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.107

AC:

156549

AN:

1461796

Hom.:

9825

Cov.:

AF XY:

0.105

AC XY:

76247

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.0165

AC:

553

AN:

33480

American (AMR)

AF:

0.207

AC:

9263

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0284

AC:

743

AN:

26136

East Asian (EAS)

AF:

0.000302

AC:

AN:

39700

South Asian (SAS)

AF:

0.0404

AC:

3487

AN:

86258

European-Finnish (FIN)

AF:

0.198

AC:

10581

AN:

53344

Middle Eastern (MID)

AF:

0.0220

AC:

127

AN:

5768

European-Non Finnish (NFE)

AF:

0.114

AC:

126398

AN:

1111992

Other (OTH)

AF:

0.0892

AC:

5385

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

8546

17091

25637

34182

42728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4476

8952

13428

17904

22380

<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:

0.0910

AC:

13848

AN:

152118

Hom.:

943

Cov.:

AF XY:

0.0934

AC XY:

6942

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0208

AC:

862

AN:

41524

American (AMR)

AF:

0.149

AC:

2282

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

AN:

3472

East Asian (EAS)

AF:

0.00155

AC:

AN:

5168

South Asian (SAS)

AF:

0.0353

AC:

170

AN:

4822

European-Finnish (FIN)

AF:

0.205

AC:

2177

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7904

AN:

67948

Other (OTH)

AF:

0.0716

AC:

151

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

605

1209

1814

2418

3023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.102

Hom.:

4486

Bravo

AF:

0.0849

TwinsUK

AF:

0.111

AC:

410

ALSPAC

AF:

0.105

AC:

403

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.108

AC:

925

ExAC

AF:

0.100

AC:

12142

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.0967

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ICAM1-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.76

MetaRNN

Benign

0.00081

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PhyloP100

2.7

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.087

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.19

MutPred

0.24

Gain of solvent accessibility (P = 0.0128);

MPC

0.69

ClinPred

0.078

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.58

Mutation Taster

=78/22

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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