Genetic Variant ICAM1:p.Lys56Met (chr19-10274864-A-T) – 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.167A>T(p.Lys56Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,614,154 control chromosomes in the GnomAD database, including 2,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).

Frequency

Genomes: 𝑓 0.070 ( 1056 hom., cov: 32)

Exomes 𝑓: 0.012 ( 1120 hom. )

Consequence

ICAM1
NM_000201.3 missense

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:1

Conservation

PhyloP100: -4.26

Publications

103 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=0.004842013).

BP6

Variant 19-10274864-A-T is Benign according to our data. Variant chr19-10274864-A-T is described in ClinVar as Benign|risk_factor. ClinVar VariationId is 14661.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM1	NM_000201.3	MANE Select	c.167A>T	p.Lys56Met	missense	Exon 2 of 7	NP_000192.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ICAM1	ENST00000264832.8	TSL:1 MANE Select	c.167A>T	p.Lys56Met	missense	Exon 2 of 7	ENSP00000264832.2
ICAM1	ENST00000902798.1		c.167A>T	p.Lys56Met	missense	Exon 2 of 6	ENSP00000572857.1
ICAM1	ENST00000588645.1	TSL:2	c.167A>T	p.Lys56Met	missense	Exon 2 of 4	ENSP00000465680.1

Frequencies

GnomAD3 genomes

AF:

0.0704

AC:

10706

AN:

152148

Hom.:

1053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.0547

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.0593

GnomAD2 exomes

AF:

0.0279

AC:

7015

AN:

251466

AF XY:

0.0238

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.0537

Gnomad FIN exome

AF:

0.0403

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0122

AC:

17814

AN:

1461888

Hom.:

1120

Cov.:

AF XY:

0.0117

AC XY:

8506

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.232

AC:

7755

AN:

33478

American (AMR)

AF:

0.0132

AC:

592

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

369

AN:

26136

East Asian (EAS)

AF:

0.0654

AC:

2598

AN:

39700

South Asian (SAS)

AF:

0.0164

AC:

1415

AN:

86258

European-Finnish (FIN)

AF:

0.0367

AC:

1962

AN:

53418

Middle Eastern (MID)

AF:

0.0251

AC:

145

AN:

5768

European-Non Finnish (NFE)

AF:

0.00145

AC:

1611

AN:

1112012

Other (OTH)

AF:

0.0226

AC:

1367

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1004

2008

3011

4015

5019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.0704

AC:

10727

AN:

152266

Hom.:

1056

Cov.:

AF XY:

0.0711

AC XY:

5293

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.220

AC:

9138

AN:

41546

American (AMR)

AF:

0.0271

AC:

415

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.0547

AC:

283

AN:

5178

South Asian (SAS)

AF:

0.0176

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0441

AC:

468

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00247

AC:

168

AN:

68018

Other (OTH)

AF:

0.0587

AC:

124

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

448

896

1344

1792

2240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0148

Hom.:

119

Bravo

AF:

0.0765

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.212

AC:

934

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.0309

AC:

3758

Asia WGS

AF:

0.0520

AC:

181

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign; risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ICAM1-related disorder (1)

Malaria, cerebral, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.033

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.068

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.077

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

-4.3

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Benign

0.090

Sift

Benign

0.078

Sift4G

Benign

0.10

Polyphen

0.065

Vest4

0.071

MPC

0.27

ClinPred

0.0060

GERP RS

-5.4

Varity_R

0.43

gMVP

0.48

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over