rs5498

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000201.3(ICAM1):c.1405A>G(p.Lys469Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,062 control chromosomes in the GnomAD database, including 148,506 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 Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.37 ( 11682 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136824 hom. )

Consequence

ICAM1
NM_000201.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.186

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=1.9145012E-4).

BP6

Variant 19-10285007-A-G is Benign according to our data. Variant chr19-10285007-A-G is described in ClinVar as [Benign]. Clinvar id is 3060077.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-10285007-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3 link	c.1405A>G	p.Lys469Glu	missense_variant	Exon 6 of 7	ENST00000264832.8	NP_000192.2	P05362A0A384MEK5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ICAM1	ENST00000264832.8 link	c.1405A>G	p.Lys469Glu	missense_variant	Exon 6 of 7	1	NM_000201.3	ENSP00000264832.2	P05362
ICAM1	ENST00000423829.2 link	c.739A>G	p.Lys247Glu	missense_variant	Exon 4 of 5	2		ENSP00000413124.2	E7ESS4
LIMASI	ENST00000592893.1 link	n.102T>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56534

AN:

151900

Hom.:

11683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.420

GnomAD2 exomes

AF:

0.438

AC:

109733

AN:

250628

AF XY:

0.442

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.466

Gnomad EAS exome

AF:

0.275

Gnomad FIN exome

AF:

0.457

Gnomad NFE exome

AF:

0.432

Gnomad OTH exome

AF:

0.447

GnomAD4 exome

AF:

0.429

AC:

626242

AN:

1461044

Hom.:

136824

Cov.:

AF XY:

0.431

AC XY:

313016

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.173

AC:

5771

AN:

33448

Gnomad4 AMR exome

AF:

0.586

AC:

26103

AN:

44530

Gnomad4 ASJ exome

AF:

0.462

AC:

12051

AN:

26112

Gnomad4 EAS exome

AF:

0.342

AC:

13563

AN:

39658

Gnomad4 SAS exome

AF:

0.487

AC:

41946

AN:

86192

Gnomad4 FIN exome

AF:

0.454

AC:

24217

AN:

53388

Gnomad4 NFE exome

AF:

0.427

AC:

474821

AN:

1111676

Gnomad4 Remaining exome

AF:

0.421

AC:

25401

AN:

60350

Heterozygous variant carriers

20435

40870

61304

81739

102174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

14460

28920

43380

57840

72300

<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:

0.372

AC:

56537

AN:

152018

Hom.:

11682

Cov.:

AF XY:

0.376

AC XY:

27951

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.185

AC:

0.184975

AN:

0.184975

Gnomad4 AMR

AF:

0.500

AC:

0.500327

AN:

0.500327

Gnomad4 ASJ

AF:

0.473

AC:

0.472607

AN:

0.472607

Gnomad4 EAS

AF:

0.287

AC:

0.286822

AN:

0.286822

Gnomad4 SAS

AF:

0.479

AC:

0.478821

AN:

0.478821

Gnomad4 FIN

AF:

0.460

AC:

0.460499

AN:

0.460499

Gnomad4 NFE

AF:

0.433

AC:

0.433043

AN:

0.433043

Gnomad4 OTH

AF:

0.420

AC:

0.420304

AN:

0.420304

Heterozygous variant carriers

1712

3425

5137

6850

8562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.416

Hom.:

64962

Bravo

AF:

0.369

TwinsUK

AF:

0.412

AC:

1526

ALSPAC

AF:

0.422

AC:

1628

ESP6500AA

AF:

0.193

AC:

849

ESP6500EA

AF:

0.431

AC:

3708

ExAC

AF:

0.428

AC:

51923

Asia WGS

AF:

0.402

AC:

1400

AN:

3478

EpiCase

AF:

0.439

EpiControl

AF:

0.442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ICAM1-related disorder

Benign:1

Oct 17, 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

0.055

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.5

DANN

Benign

0.32

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.042

T;T

MetaRNN

Benign

0.00019

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.5

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.018

MPC

0.22

ClinPred

0.00058

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over