Genetic Variant ICAM1:c.*1275C>T (chr19-10286562-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000201.3(ICAM1):c.*1275C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 166,128 control chromosomes in the GnomAD database, including 7,229 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 0.29 ( 6760 hom., cov: 29)

Exomes 𝑓: 0.22 ( 469 hom. )

Consequence

ICAM1
NM_000201.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

Publications

81 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:

ICAM4-AS1 (HGNC:55990): (ICAM4 antisense RNA 1)

ICAM4-AS1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3 link	c.*1275C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000264832.8	NP_000192.2
ICAM4-AS1	NR_186335.1 link	n.2458G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ICAM1	ENST00000264832.8 link	c.*1275C>T	3_prime_UTR_variant	Exon 7 of 7	1	NM_000201.3	ENSP00000264832.2
ICAM4-AS1	ENST00000589379.1 link	n.2458G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
LIMASI	ENST00000715961.1 link	n.395+3857G>A	intron_variant	Intron 1 of 2
ICAM4-AS1	ENST00000724881.1 link	n.380-623G>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

43905

AN:

151072

Hom.:

6751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.220

AC:

3279

AN:

14938

Hom.:

469

Cov.:

AF XY:

0.222

AC XY:

1673

AN XY:

7532

show subpopulations

African (AFR)

AF:

0.312

AC:

179

AN:

574

American (AMR)

AF:

0.126

AC:

AN:

428

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

128

AN:

588

East Asian (EAS)

AF:

0.0638

AC:

AN:

1192

South Asian (SAS)

AF:

0.157

AC:

AN:

140

European-Finnish (FIN)

AF:

0.189

AC:

173

AN:

916

Middle Eastern (MID)

AF:

0.197

AC:

AN:

European-Non Finnish (NFE)

AF:

0.241

AC:

2424

AN:

10070

Other (OTH)

AF:

0.218

AC:

208

AN:

954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

124

249

373

498

622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.291

AC:

43957

AN:

151190

Hom.:

6760

Cov.:

AF XY:

0.286

AC XY:

21081

AN XY:

73782

show subpopulations

African (AFR)

AF:

0.362

AC:

14913

AN:

41160

American (AMR)

AF:

0.218

AC:

3304

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

985

AN:

3470

East Asian (EAS)

AF:

0.103

AC:

532

AN:

5154

South Asian (SAS)

AF:

0.242

AC:

1156

AN:

4786

European-Finnish (FIN)

AF:

0.257

AC:

2647

AN:

10306

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19587

AN:

67840

Other (OTH)

AF:

0.292

AC:

612

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1534

3067

4601

6134

7668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.282

Hom.:

21593

Bravo

AF:

0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.8

(source)

DANN

Benign

0.60

PhyloP100

0.12

PromoterAI

0.20

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over