rs281428

Positions:

• chr19-10277648-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
ICAM1	NM_000201.3	c.331+2620C>T		intron_variant		ENST00000264832.8
LIMASI	XR_007067138.1	n.130+5673G>A		intron_variant, non_coding_transcript_variant
LIMASI	XR_007067137.1	n.130+5673G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM1	ENST00000264832.8	c.331+2620C>T		intron_variant		1	NM_000201.3	P1
LIMASI	ENST00000592893.1	n.141+7320G>A		intron_variant, non_coding_transcript_variant		3
ICAM1	ENST00000423829.2	c.67+6422C>T		intron_variant		2
ICAM1	ENST00000588645.1	c.331+2620C>T		intron_variant		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

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.432

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

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: rs281428; hg19: chr19-10388324;