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GeneBe

rs1799969

Variant summary

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

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. 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 0.091 ( 943 hom., cov: 32)
Exomes 𝑓: 0.11 ( 9825 hom. )

Consequence

ICAM1
NM_000201.3 missense

Scores

1
3
14

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.71
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=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 id is 3060438.Status of the report is criteria_provided_single_submitter, 1 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/exons MANE UniProt
ICAM1NM_000201.3 linkuse as main transcriptc.721G>A p.Gly241Arg missense_variant 4/7 ENST00000264832.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ICAM1ENST00000264832.8 linkuse as main transcriptc.721G>A p.Gly241Arg missense_variant 4/71 NM_000201.3 P1
LIMASIENST00000592893.1 linkuse as main transcriptn.141+852C>T intron_variant, non_coding_transcript_variant 3
ICAM1ENST00000423829.2 linkuse as main transcriptc.68-13G>A splice_polypyrimidine_tract_variant, intron_variant 2
ICAM1ENST00000592686.1 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0911
AC:
13842
AN:
152000
Hom.:
942
Cov.:
32
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
GnomAD3 exomes
AF:
0.107
AC:
26844
AN:
251270
Hom.:
2108
AF XY:
0.102
AC XY:
13853
AN XY:
135830
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 SAS exome
AF:
0.0369
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.:
33
AF XY:
0.105
AC XY:
76247
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.0165
Gnomad4 AMR exome
AF:
0.207
Gnomad4 ASJ exome
AF:
0.0284
Gnomad4 EAS exome
AF:
0.000302
Gnomad4 SAS exome
AF:
0.0404
Gnomad4 FIN exome
AF:
0.198
Gnomad4 NFE exome
AF:
0.114
Gnomad4 OTH exome
AF:
0.0892
GnomAD4 genome
AF:
0.0910
AC:
13848
AN:
152118
Hom.:
943
Cov.:
32
AF XY:
0.0934
AC XY:
6942
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0208
Gnomad4 AMR
AF:
0.149
Gnomad4 ASJ
AF:
0.0276
Gnomad4 EAS
AF:
0.00155
Gnomad4 SAS
AF:
0.0353
Gnomad4 FIN
AF:
0.205
Gnomad4 NFE
AF:
0.116
Gnomad4 OTH
AF:
0.0716
Alfa
AF:
0.100
Hom.:
2213
Bravo
AF:
0.0849
TwinsUK
AF:
0.111
AC:
410
ALSPAC
AF:
0.105
AC:
403
ESP6500AA
AF:
0.0207
AC:
91
ESP6500EA
AF:
0.108
AC:
925
ExAC
AF:
0.100
AC:
12142
Asia WGS
AF:
0.0230
AC:
81
AN:
3478
EpiCase
AF:
0.102
EpiControl
AF:
0.0967

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 18, 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
0.18
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.58
Cadd
Pathogenic
26
Dann
Uncertain
0.99
DEOGEN2
Benign
0.30
T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.76
T
MetaRNN
Benign
0.00081
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.45
T
PROVEAN
Pathogenic
-5.0
D
REVEL
Benign
0.087
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.19
MutPred
0.24
Gain of solvent accessibility (P = 0.0128);
MPC
0.69
ClinPred
0.078
T
GERP RS
2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.34
gMVP
0.58

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

LitVar

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

Other links and lift over

dbSNP: rs1799969; hg19: chr19-10394792; COSMIC: COSV53424452; COSMIC: COSV53424452; API