Genetic Variant ICAM1:p.Asp98Asn (chr19-10274989-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000201.3(ICAM1):c.292G>A(p.Asp98Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,614,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 1 hom. )

Consequence

ICAM1
NM_000201.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.42

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036714107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3 link	c.292G>A	p.Asp98Asn	missense_variant	Exon 2 of 7	ENST00000264832.8	NP_000192.2	P05362A0A384MEK5
LIMASI	XR_007067137.1 link	n.131-8195C>T		intron_variant	Intron 1 of 3
LIMASI	XR_007067138.1 link	n.131-8195C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ICAM1	ENST00000264832.8 link	c.292G>A	p.Asp98Asn	missense_variant	Exon 2 of 7	1	NM_000201.3	ENSP00000264832.2	P05362
ICAM1	ENST00000588645.1 link	c.292G>A	p.Asp98Asn	missense_variant	Exon 2 of 4	2		ENSP00000465680.1	K7EKL8
ICAM1	ENST00000423829.2 link	c.67+3763G>A		intron_variant	Intron 1 of 4	2		ENSP00000413124.2	E7ESS4
LIMASI	ENST00000592893.1 link	n.141+9979C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251220

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.0000971

AC:

142

AN:

1461710

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0020

DANN

Benign

0.71

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

0.34

N;.

REVEL

Benign

0.017

Sift

Benign

0.48

T;.

Sift4G

Benign

0.51

T;T

Polyphen

0.013

B;.

Vest4

0.078

MutPred

0.44

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.32

MPC

0.15

ClinPred

0.018

GERP RS

-8.1

Varity_R

0.40

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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