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GeneBe

rs5498

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 11682 hom., cov: 32)
Exomes 𝑓: 0.43 ( 136824 hom. )

Consequence

ICAM1
NM_000201.3 missense

Scores

18

Clinical Significance

Benign criteria provided, single submitter 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]
LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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/exons MANE UniProt
ICAM1NM_000201.3 linkuse as main transcriptc.1405A>G p.Lys469Glu missense_variant 6/7 ENST00000264832.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ICAM1ENST00000264832.8 linkuse as main transcriptc.1405A>G p.Lys469Glu missense_variant 6/71 NM_000201.3 P1
LIMASIENST00000592893.1 linkuse as main transcriptn.102T>C non_coding_transcript_exon_variant 1/33
ICAM1ENST00000423829.2 linkuse as main transcriptc.739A>G p.Lys247Glu missense_variant 4/52

Frequencies

GnomAD3 genomes
AF:
0.372
AC:
56534
AN:
151900
Hom.:
11683
Cov.:
32
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
GnomAD3 exomes
AF:
0.438
AC:
109733
AN:
250628
Hom.:
25472
AF XY:
0.442
AC XY:
59930
AN XY:
135520
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 SAS exome
AF:
0.488
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.:
53
AF XY:
0.431
AC XY:
313016
AN XY:
726776
show subpopulations
Gnomad4 AFR exome
AF:
0.173
Gnomad4 AMR exome
AF:
0.586
Gnomad4 ASJ exome
AF:
0.462
Gnomad4 EAS exome
AF:
0.342
Gnomad4 SAS exome
AF:
0.487
Gnomad4 FIN exome
AF:
0.454
Gnomad4 NFE exome
AF:
0.427
Gnomad4 OTH exome
AF:
0.421
GnomAD4 genome
AF:
0.372
AC:
56537
AN:
152018
Hom.:
11682
Cov.:
32
AF XY:
0.376
AC XY:
27951
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.185
Gnomad4 AMR
AF:
0.500
Gnomad4 ASJ
AF:
0.473
Gnomad4 EAS
AF:
0.287
Gnomad4 SAS
AF:
0.479
Gnomad4 FIN
AF:
0.460
Gnomad4 NFE
AF:
0.433
Gnomad4 OTH
AF:
0.420
Alfa
AF:
0.425
Hom.:
35039
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

ICAM1-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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
T
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
N
LIST_S2
Benign
0.042
T;T
MetaRNN
Benign
0.00019
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-1.5
N;.
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.30
T
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
T
GERP RS
-2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.037
gMVP
0.31

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.

Other links and lift over

dbSNP: rs5498; hg19: chr19-10395683; COSMIC: COSV53424462; COSMIC: COSV53424462; API