rs281428

Variant names:

• chr19-10277648-C-T
• rs281428
• NM_000201.3:c.331+2620C>T

Variant summary

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

The NM_000201.3(ICAM1):​c.331+2620C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,562 control chromosomes in the GnomAD database, including 15,908 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 0.44 (15908 hom., cov: 30)
• Consequence: ICAM1 NM_000201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• Publications: 8 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3	c.331+2620C>T		intron_variant	Intron 2 of 6	ENST00000264832.8	NP_000192.2
LIMASI	XR_007067137.1	n.130+5673G>A		intron_variant	Intron 1 of 3
LIMASI	XR_007067138.1	n.130+5673G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8	c.331+2620C>T		intron_variant	Intron 2 of 6	1	NM_000201.3	ENSP00000264832.2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66374 AN: 151444 Hom.: 15879 Cov.: 30

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.438 AC: 66450 AN: 151562 Hom.: 15908 Cov.: 30 AF XY: 0.432 AC XY: 32008 AN XY: 74036

African (AFR) AF: 0.633 AC: 26152 AN: 41282

American (AMR) AF: 0.301 AC: 4578 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1500 AN: 3468

East Asian (EAS) AF: 0.102 AC: 524 AN: 5138

South Asian (SAS) AF: 0.314 AC: 1506 AN: 4802

European-Finnish (FIN) AF: 0.373 AC: 3912 AN: 10478

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27099 AN: 67898

Other (OTH) AF: 0.432 AC: 909 AN: 2102

Alfa AF: 0.423 Hom.: 1765

Bravo AF: 0.440

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.60
PhyloP100		-3.0
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: rs281428; hg19: chr19-10388324;