rs5498

Variant names:

• chr19-10285007-A-G
• rs5498
• NM_000201.3:c.1405A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-10285007-A-G
• chr19-10285007-A-T

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.1405A>G​(p.Lys469Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,062 control chromosomes in the GnomAD database, including 148,506 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.37 (11682 hom., cov: 32)
  • Exomes 𝑓: 0.43 (136824 hom.)
• Consequence: ICAM1 NM_000201.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.186
• Publications: 487 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=1.9145012E-4).
• BP6: Variant 19-10285007-A-G is Benign according to our data. Variant chr19-10285007-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060077.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3	c.1405A>G	p.Lys469Glu	missense_variant	Exon 6 of 7	ENST00000264832.8	NP_000192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8	c.1405A>G	p.Lys469Glu	missense_variant	Exon 6 of 7	1	NM_000201.3	ENSP00000264832.2
ICAM1	ENST00000423829.2	c.739A>G	p.Lys247Glu	missense_variant	Exon 4 of 5	2		ENSP00000413124.2
LIMASI	ENST00000592893.1	n.102T>C		non_coding_transcript_exon_variant	Exon 1 of 3	3
LIMASI	ENST00000715961.1	n.395+5412T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56534 AN: 151900 Hom.: 11683 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.420

GnomAD2 exomes AF: 0.438 AC: 109733 AN: 250628 AF XY: 0.442

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.275

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.432

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.429 AC: 626242 AN: 1461044 Hom.: 136824 Cov.: 53 AF XY: 0.431 AC XY: 313016 AN XY: 726776

African (AFR) AF: 0.173 AC: 5771 AN: 33448

American (AMR) AF: 0.586 AC: 26103 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 12051 AN: 26112

East Asian (EAS) AF: 0.342 AC: 13563 AN: 39658

South Asian (SAS) AF: 0.487 AC: 41946 AN: 86192

European-Finnish (FIN) AF: 0.454 AC: 24217 AN: 53388

Middle Eastern (MID) AF: 0.416 AC: 2369 AN: 5690

European-Non Finnish (NFE) AF: 0.427 AC: 474821 AN: 1111676

Other (OTH) AF: 0.421 AC: 25401 AN: 60350

GnomAD4 genome AF: 0.372 AC: 56537 AN: 152018 Hom.: 11682 Cov.: 32 AF XY: 0.376 AC XY: 27951 AN XY: 74290

African (AFR) AF: 0.185 AC: 7675 AN: 41492

American (AMR) AF: 0.500 AC: 7639 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1639 AN: 3468

East Asian (EAS) AF: 0.287 AC: 1480 AN: 5160

South Asian (SAS) AF: 0.479 AC: 2306 AN: 4816

European-Finnish (FIN) AF: 0.460 AC: 4873 AN: 10582

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29414 AN: 67924

Other (OTH) AF: 0.420 AC: 886 AN: 2108

Alfa AF: 0.416 Hom.: 64962

Bravo AF: 0.369

TwinsUK AF: 0.412 AC: 1526

ALSPAC AF: 0.422 AC: 1628

ESP6500AA AF: 0.193 AC: 849

ESP6500EA AF: 0.431 AC: 3708

ExAC AF: 0.428 AC: 51923

Asia WGS AF: 0.402 AC: 1400 AN: 3478

EpiCase AF: 0.439

EpiControl AF: 0.442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ICAM1-related disorder Benign:1

Oct 17, 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 v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.32
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.042	T;T
MetaRNN	Benign	0.00019	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.5	N;.
PhyloP100		0.19
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.020
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.018
MPC		0.22
ClinPred		0.00058	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.037
gMVP		0.31
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs5498; hg19: chr19-10395683; COSMIC: COSV53424462; COSMIC: COSV53424462;