rs281430

chr19-10279261-A-G

Variant summary

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

The NM_000201.3(ICAM1):c.332-4220A>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

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=-0.91).
• 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/exons	MANE	UniProt
ICAM1	NM_000201.3	c.332-4220A>G		intron_variant		ENST00000264832.8
LIMASI	XR_007067138.1	n.130+4060T>C		intron_variant, non_coding_transcript_variant
LIMASI	XR_007067137.1	n.130+4060T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM1	ENST00000264832.8	c.332-4220A>G		intron_variant		1	NM_000201.3	P1
LIMASI	ENST00000592893.1	n.141+5707T>C		intron_variant, non_coding_transcript_variant		3
ICAM1	ENST00000423829.2	c.68-4868A>G		intron_variant		2
ICAM1	ENST00000588645.1	c.332-4220A>G		intron_variant		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

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.442

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

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: rs281430; hg19: chr19-10389937;