Genetic Variant ICAM1:c.-9A>C (chr19-10271151-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.610

Publications

16 publications found

Variant links:

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]

ICAM1 links:

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

LIMASI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00547

AC XY:

3973

AN XY:

726274

show subpopulations

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:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.000523

AC:

AN:

86040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53150

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

5286

European-Non Finnish (NFE)

AF:

0.000392

AC:

436

AN:

1111488

Other (OTH)

AF:

0.0149

AC:

897

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

391

782

1174

1565

1956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0629

AC:

9582

AN:

152218

Hom.:

997

Cov.:

AF XY:

0.0610

AC XY:

4544

AN XY:

74434

show subpopulations

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:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68008

Other (OTH)

AF:

0.0525

AC:

111

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

395

791

1186

1582

1977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0330

Hom.:

286

Bravo

AF:

0.0724

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000831

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ICAM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.0

(source)

DANN

Benign

0.40

PhyloP100

-0.61

PromoterAI

0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over