rs281432

Variant names:

• chr19-10279982-C-G
• rs281432
• NM_000201.3:c.332-3499C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000201.3(ICAM1):​c.332-3499C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,894 control chromosomes in the GnomAD database, including 21,440 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 0.52 (21440 hom., cov: 31)
• Consequence: ICAM1 NM_000201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3	c.332-3499C>G		intron_variant	Intron 2 of 6	ENST00000264832.8	NP_000192.2
LIMASI	XR_007067137.1	n.130+3339G>C		intron_variant	Intron 1 of 3
LIMASI	XR_007067138.1	n.130+3339G>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8	c.332-3499C>G		intron_variant	Intron 2 of 6	1	NM_000201.3	ENSP00000264832.2
ICAM1	ENST00000423829.2	c.68-4147C>G		intron_variant	Intron 1 of 4	2		ENSP00000413124.2
ICAM1	ENST00000588645.1	c.332-3499C>G		intron_variant	Intron 2 of 3	2		ENSP00000465680.1
LIMASI	ENST00000592893.1	n.141+4986G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78785 AN: 151776 Hom.: 21412 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.519 AC: 78859 AN: 151894 Hom.: 21440 Cov.: 31 AF XY: 0.517 AC XY: 38390 AN XY: 74212

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.537

Alfa AF: 0.487 Hom.: 2576

Bravo AF: 0.523

Asia WGS AF: 0.488 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs281432; hg19: chr19-10390658;