19-10274864-A-T

Variant summary

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

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

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 criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -4.26

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 made for transcript

Verdict is Benign. Variant got -14 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]. Clinvar id is 14661.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ICAM1	NM_000201.3 linkuse as main transcript	c.167A>T	p.Lys56Met	missense_variant	2/7	ENST00000264832.8
LIMASI	XR_007067138.1 linkuse as main transcript	n.131-8070T>A		intron_variant, non_coding_transcript_variant
LIMASI	XR_007067137.1 linkuse as main transcript	n.131-8070T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ICAM1	ENST00000264832.8 linkuse as main transcript	c.167A>T	p.Lys56Met	missense_variant	2/7	1	NM_000201.3	P1
LIMASI	ENST00000592893.1 linkuse as main transcript	n.141+10104T>A		intron_variant, non_coding_transcript_variant		3
ICAM1	ENST00000588645.1 linkuse as main transcript	c.167A>T	p.Lys56Met	missense_variant	2/4	2
ICAM1	ENST00000423829.2 linkuse as main transcript	c.67+3638A>T		intron_variant		2

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

GnomAD3 exomes

AF:

0.0279

AC:

7015

AN:

251466

Hom.:

485

AF XY:

0.0238

AC XY:

3233

AN XY:

135922

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 SAS exome

AF:

0.0161

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

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.0654

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.0367

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.0226

GnomAD4 genome

AF:

0.0704

AC:

10727

AN:

152266

Hom.:

1056

Cov.:

AF XY:

0.0711

AC XY:

5293

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.0547

Gnomad4 SAS

AF:

0.0176

Gnomad4 FIN

AF:

0.0441

Gnomad4 NFE

AF:

0.00247

Gnomad4 OTH

AF:

0.0587

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

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ICAM1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2019

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). -

Malaria, cerebral, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

Cadd

Benign

0.033

Dann

Benign

0.44

DEOGEN2

Benign

0.068

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.077

T;T

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.090

Sift

Benign

0.078

T;.

Sift4G

Benign

0.10

T;T

Polyphen

0.065

B;.

Vest4

0.071

MPC

0.27

ClinPred

0.0060

GERP RS

-5.4

Varity_R

0.43

gMVP

0.48

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over