rs5490

Variant names:

• chr19-10271151-A-C
• rs5490
• NM_000201.3:c.-9A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000201.3(ICAM1):​c.-9A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,612,170 control chromosomes in the GnomAD database, including 1,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.063 (997 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (908 hom.)
• Consequence: ICAM1 NM_000201.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.610
• Publications: 16 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 19-10271151-A-C is Benign according to our data. Variant chr19-10271151-A-C is described in ClinVar as Benign. ClinVar VariationId is 3056696.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000201.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM1	NM_000201.3	MANE Select	c.-9A>C		5_prime_UTR	Exon 1 of 7	NP_000192.2	A0A384MEK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM1	ENST00000264832.8	TSL:1 MANE Select	c.-9A>C		5_prime_UTR	Exon 1 of 7	ENSP00000264832.2	P05362
	ICAM1	ENST00000902798.1		c.-9A>C		5_prime_UTR	Exon 1 of 6	ENSP00000572857.1
	ICAM1	ENST00000935832.1		c.-9A>C		5_prime_UTR	Exon 1 of 6	ENSP00000605891.1

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9572 AN: 152100 Hom.: 995 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0531

GnomAD2 exomes AF: 0.0159 AC: 3922 AN: 246402 AF XY: 0.0116

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.00997

Gnomad ASJ exome AF: 0.00182

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000667

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00647 AC: 9447 AN: 1459952 Hom.: 908 Cov.: 30 AF XY: 0.00547 AC XY: 3973 AN XY: 726274

African (AFR) AF: 0.223 AC: 7467 AN: 33432

American (AMR) AF: 0.0115 AC: 512 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00127 AC: 33 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.000523 AC: 45 AN: 86040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53150

Middle Eastern (MID) AF: 0.0108 AC: 57 AN: 5286

European-Non Finnish (NFE) AF: 0.000392 AC: 436 AN: 1111488

Other (OTH) AF: 0.0149 AC: 897 AN: 60228

GnomAD4 genome AF: 0.0629 AC: 9582 AN: 152218 Hom.: 997 Cov.: 32 AF XY: 0.0610 AC XY: 4544 AN XY: 74434

African (AFR) AF: 0.217 AC: 9027 AN: 41518

American (AMR) AF: 0.0256 AC: 391 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68008

Other (OTH) AF: 0.0525 AC: 111 AN: 2114

Alfa AF: 0.0330 Hom.: 286

Bravo AF: 0.0724

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000831

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ICAM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.40
PhyloP100		-0.61
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs5490; hg19: chr19-10381827;