Variant rs1801714 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000201.3(ICAM1):c.1055C>T(p.Pro352Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,613,982 control chromosomes in the GnomAD database, including 684 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.021 ( 39 hom., cov: 32)

Exomes 𝑓: 0.028 ( 645 hom. )

Consequence

ICAM1
NM_000201.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.61

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035290718).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3258/152220) while in subpopulation NFE AF= 0.0295 (2009/67992). AF 95% confidence interval is 0.0285. There are 39 homozygotes in gnomad4. There are 1532 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICAM1	NM_000201.3 linkuse as main transcript	c.1055C>T	p.Pro352Leu	missense_variant	5/7	ENST00000264832.8	NP_000192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ICAM1	ENST00000264832.8 linkuse as main transcript	c.1055C>T	p.Pro352Leu	missense_variant	5/7	1	NM_000201.3	ENSP00000264832	P1
LIMASI	ENST00000592893.1 linkuse as main transcript	n.141+436G>A		intron_variant, non_coding_transcript_variant		3
ICAM1	ENST00000423829.2 linkuse as main transcript	c.389C>T	p.Pro130Leu	missense_variant	3/5	2		ENSP00000413124

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3257

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00999

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0295

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0215

AC:

5356

AN:

249536

Hom.:

AF XY:

0.0212

AC XY:

2878

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.00919

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0500

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00552

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0298

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0277

AC:

40425

AN:

1461762

Hom.:

645

Cov.:

AF XY:

0.0268

AC XY:

19467

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00795

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.0494

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00543

Gnomad4 FIN exome

AF:

0.0231

Gnomad4 NFE exome

AF:

0.0311

Gnomad4 OTH exome

AF:

0.0290

GnomAD4 genome

AF:

0.0214

AC:

3258

AN:

152220

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1532

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00999

Gnomad4 AMR

AF:

0.0248

Gnomad4 ASJ

AF:

0.0487

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.0295

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0290

Hom.:

157

Bravo

AF:

0.0224

TwinsUK

AF:

0.0329

AC:

122

ALSPAC

AF:

0.0314

AC:

121

ESP6500AA

AF:

0.00954

AC:

ESP6500EA

AF:

0.0292

AC:

251

ExAC

AF:

0.0216

AC:

2615

EpiCase

AF:

0.0334

EpiControl

AF:

0.0324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.3

DANN

Benign

0.97

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.057

Sift

Benign

0.072

T;T

Sift4G

Benign

0.068

T;D

Polyphen

0.96

D;D

Vest4

0.17

MPC

0.27

ClinPred

0.042

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.36

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over