rs281430

Variant names:

• chr19-10279261-A-G
• rs281430
• NM_000201.3:c.332-4220A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000201.3(ICAM1):​c.332-4220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,380 control chromosomes in the GnomAD database, including 16,350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16350 hom., cov: 30)
• Consequence: ICAM1 NM_000201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.968
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3	c.332-4220A>G		intron_variant	Intron 2 of 6	ENST00000264832.8	NP_000192.2
LIMASI	XR_007067137.1	n.130+4060T>C		intron_variant	Intron 1 of 3
LIMASI	XR_007067138.1	n.130+4060T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8	c.332-4220A>G		intron_variant	Intron 2 of 6	1	NM_000201.3	ENSP00000264832.2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67778 AN: 151262 Hom.: 16324 Cov.: 30

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.448 AC: 67851 AN: 151380 Hom.: 16350 Cov.: 30 AF XY: 0.444 AC XY: 32854 AN XY: 73952

African (AFR) AF: 0.634 AC: 26113 AN: 41190

American (AMR) AF: 0.304 AC: 4629 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1558 AN: 3456

East Asian (EAS) AF: 0.164 AC: 845 AN: 5160

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4808

European-Finnish (FIN) AF: 0.414 AC: 4340 AN: 10486

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.404 AC: 27403 AN: 67764

Other (OTH) AF: 0.442 AC: 929 AN: 2100

Alfa AF: 0.430 Hom.: 3261

Bravo AF: 0.448

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.48
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs281430; hg19: chr19-10389937;