rs5030400

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000201.3(ICAM1):c.1432C>T(p.Arg478Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,614,078 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R478Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 18 hom. )

Consequence

ICAM1
NM_000201.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.747

Publications

24 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006729126).

BP6

Variant 19-10285120-C-T is Benign according to our data. Variant chr19-10285120-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 828004.

BS2

High Homozygotes in GnomAdExome4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000201.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM1	NM_000201.3	MANE Select	c.1432C>T	p.Arg478Trp	missense	Exon 7 of 7	NP_000192.2	A0A384MEK5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ICAM1	ENST00000264832.8	TSL:1 MANE Select	c.1432C>T	p.Arg478Trp	missense	Exon 7 of 7	ENSP00000264832.2	P05362
ICAM1	ENST00000902798.1		c.1186C>T	p.Arg396Trp	missense	Exon 6 of 6	ENSP00000572857.1
ICAM1	ENST00000935832.1		c.1168C>T	p.Arg390Trp	missense	Exon 6 of 6	ENSP00000605891.1

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

593

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00592

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00377

AC:

947

AN:

251132

AF XY:

0.00393

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00620

Gnomad NFE exome

AF:

0.00530

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00510

AC:

7454

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

3637

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33480

American (AMR)

AF:

0.00306

AC:

137

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.000345

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00209

AC:

180

AN:

86244

European-Finnish (FIN)

AF:

0.00580

AC:

310

AN:

53414

Middle Eastern (MID)

AF:

0.000869

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00589

AC:

6548

AN:

1111966

Other (OTH)

AF:

0.00363

AC:

219

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

416

832

1249

1665

2081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

242

484

726

968

1210

<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:

0.00389

AC:

593

AN:

152296

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

284

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

41546

American (AMR)

AF:

0.00373

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00248

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00584

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00592

AC:

403

AN:

68030

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00427

Hom.:

Bravo

AF:

0.00373

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.00410

AC:

498

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00492

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Malaria, susceptibility to (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.59

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-0.75

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.0

REVEL

Benign

0.036

Sift

Benign

0.19

Sift4G

Benign

0.065

Polyphen

0.99

Vest4

0.19

MVP

0.51

MPC

0.60

ClinPred

0.037

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.48

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over