rs5030364

chr19-10280033-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000201.3(ICAM1):c.332-3448T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 152,278 control chromosomes in the GnomAD database, including 9 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 0.0059 (9 hom., cov: 31)
• Consequence: ICAM1 NM_000201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586

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=-0.88).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00588 (896/152278) while in subpopulation AFR AF= 0.0204 (848/41546). AF 95% confidence interval is 0.0193. There are 9 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICAM1	NM_000201.3	c.332-3448T>A		intron_variant		ENST00000264832.8
LIMASI	XR_007067138.1	n.130+3288A>T		intron_variant, non_coding_transcript_variant
LIMASI	XR_007067137.1	n.130+3288A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM1	ENST00000264832.8	c.332-3448T>A		intron_variant		1	NM_000201.3	P1
LIMASI	ENST00000592893.1	n.141+4935A>T		intron_variant, non_coding_transcript_variant		3
ICAM1	ENST00000423829.2	c.68-4096T>A		intron_variant		2
ICAM1	ENST00000588645.1	c.332-3448T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 895 AN: 152160 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00588 AC: 896 AN: 152278 Hom.: 9 Cov.: 31 AF XY: 0.00569 AC XY: 424 AN XY: 74456

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00513 Hom.: 0

Bravo AF: 0.00674

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.31
Dann	Benign	0.41

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: rs5030364; hg19: chr19-10390709;