Variant chr19-10284116-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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 (no stars). 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

Clinical Significance

Benign no assertion criteria provided 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]

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 -13 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 no_assertion_criteria_provided, 0 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	Protein	UniProt
ICAM1	NM_000201.3 linkuse as main transcript	c.721G>A	p.Gly241Arg	missense_variant	4/7	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.721G>A	p.Gly241Arg	missense_variant	4/7	1	NM_000201.3	ENSP00000264832	P1
LIMASI	ENST00000592893.1 linkuse as main transcript	n.141+852C>T		intron_variant, non_coding_transcript_variant		3
ICAM1	ENST00000423829.2 linkuse as main transcript	c.68-13G>A		splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000413124
ICAM1	ENST00000592686.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0911

AC:

13842

AN:

152000

Hom.:

942

Cov.:

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.:

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.:

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:

ESP6500EA

AF:

0.108

AC:

925

ExAC

AF:

0.100

AC:

12142

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.0967

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ICAM1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.76

MetaRNN

Benign

0.00081

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.087

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.19

MutPred

0.24

Gain of solvent accessibility (P = 0.0128);

MPC

0.69

ClinPred

0.078

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.

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