rs281431

Variant names:

• chr19-10279269-T-C
• rs281431
• NM_000201.3:c.332-4212T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-10279269-T-C
• chr19-10279269-T-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.332-4212T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,264 control chromosomes in the GnomAD database, including 15,975 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 (15975 hom., cov: 29)
• Consequence: ICAM1 NM_000201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 6 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=-0.95).
• 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.332-4212T>C		intron_variant	Intron 2 of 6	ENST00000264832.8	NP_000192.2
LIMASI	XR_007067137.1	n.130+4052A>G		intron_variant	Intron 1 of 3
LIMASI	XR_007067138.1	n.130+4052A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8	c.332-4212T>C		intron_variant	Intron 2 of 6	1	NM_000201.3	ENSP00000264832.2

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66652 AN: 151146 Hom.: 15946 Cov.: 29

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.441 AC: 66725 AN: 151264 Hom.: 15975 Cov.: 29 AF XY: 0.435 AC XY: 32154 AN XY: 73890

African (AFR) AF: 0.634 AC: 26068 AN: 41144

American (AMR) AF: 0.302 AC: 4582 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1516 AN: 3458

East Asian (EAS) AF: 0.109 AC: 561 AN: 5150

South Asian (SAS) AF: 0.352 AC: 1686 AN: 4786

European-Finnish (FIN) AF: 0.371 AC: 3877 AN: 10464

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27255 AN: 67766

Other (OTH) AF: 0.432 AC: 907 AN: 2098

Alfa AF: 0.301 Hom.: 849

Bravo AF: 0.443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.58
DANN	Benign	0.28
PhyloP100		-2.4
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: rs281431; hg19: chr19-10389945;