19-10284116-G-A

Variant names:

• chr19-10284116-G-A
• rs1799969
• NM_000201.3:c.721G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.091 (943 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9825 hom.)
• Consequence: ICAM1 NM_000201.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.71
• Publications: 217 publications found

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]

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.721G>A	p.Gly241Arg	missense	Exon 4 of 7	NP_000192.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM1	ENST00000264832.8	TSL:1 MANE Select	c.721G>A	p.Gly241Arg	missense	Exon 4 of 7	ENSP00000264832.2
	ICAM1	ENST00000423829.2	TSL:2	c.68-13G>A		intron	N/A	ENSP00000413124.2
	LIMASI	ENST00000592893.1	TSL:3	n.141+852C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13842 AN: 152000 Hom.: 942 Cov.: 32

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

GnomAD2 exomes AF: 0.107 AC: 26844 AN: 251270 AF XY: 0.102

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 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.: 33 AF XY: 0.105 AC XY: 76247 AN XY: 727214

African (AFR) AF: 0.0165 AC: 553 AN: 33480

American (AMR) AF: 0.207 AC: 9263 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0284 AC: 743 AN: 26136

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.0404 AC: 3487 AN: 86258

European-Finnish (FIN) AF: 0.198 AC: 10581 AN: 53344

Middle Eastern (MID) AF: 0.0220 AC: 127 AN: 5768

European-Non Finnish (NFE) AF: 0.114 AC: 126398 AN: 1111992

Other (OTH) AF: 0.0892 AC: 5385 AN: 60396

GnomAD4 genome AF: 0.0910 AC: 13848 AN: 152118 Hom.: 943 Cov.: 32 AF XY: 0.0934 AC XY: 6942 AN XY: 74358

African (AFR) AF: 0.0208 AC: 862 AN: 41524

American (AMR) AF: 0.149 AC: 2282 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 96 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5168

South Asian (SAS) AF: 0.0353 AC: 170 AN: 4822

European-Finnish (FIN) AF: 0.205 AC: 2177 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7904 AN: 67948

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.102 Hom.: 4486

Bravo AF: 0.0849

TwinsUK AF: 0.111 AC: 410

ALSPAC AF: 0.105 AC: 403

ESP6500AA AF: 0.0207 AC: 91

ESP6500EA AF: 0.108 AC: 925

ExAC AF: 0.100 AC: 12142

Asia WGS AF: 0.0230 AC: 81 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.0967

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ICAM1-related disorder Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.00081	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.7
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.087
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.24		Gain of solvent accessibility (P = 0.0128)
MPC		0.69
ClinPred		0.078	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.58
Mutation Taster		=78/22	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1799969; hg19: chr19-10394792; COSMIC: COSV53424452; COSMIC: COSV53424452;