rs281434

Positions:

• chr19-10281944-A-G
• chr19-10281944-A-T

Variant summary

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

The NM_000201.3(ICAM1):​c.332-1537A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 151,766 control chromosomes in the GnomAD database, including 45,927 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 0.77 (45927 hom., cov: 30)
• Consequence: ICAM1 NM_000201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICAM1	NM_000201.3	c.332-1537A>G		intron_variant		ENST00000264832.8
LIMASI	XR_007067138.1	n.130+1377T>C		intron_variant, non_coding_transcript_variant
LIMASI	XR_007067137.1	n.130+1377T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM1	ENST00000264832.8	c.332-1537A>G		intron_variant		1	NM_000201.3	P1
LIMASI	ENST00000592893.1	n.141+3024T>C		intron_variant, non_coding_transcript_variant		3
ICAM1	ENST00000423829.2	c.68-2185A>G		intron_variant		2
ICAM1	ENST00000588645.1	c.332-1537A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117197 AN: 151650 Hom.: 45923 Cov.: 30

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.773 AC: 117249 AN: 151766 Hom.: 45927 Cov.: 30 AF XY: 0.771 AC XY: 57190 AN XY: 74148

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.797

Alfa AF: 0.759 Hom.: 2335

Bravo AF: 0.763

Asia WGS AF: 0.638 AC: 2221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.40

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: rs281434; hg19: chr19-10392620;