Genetic Variant ICAM1:c.331+39C>G (chr19-10275067-C-G) – 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.331+39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,598,608 control chromosomes in the GnomAD database, including 138,644 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 0.46 ( 18012 hom., cov: 33)

Exomes 𝑓: 0.40 ( 120632 hom. )

Consequence

ICAM1
NM_000201.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.372

Publications

12 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 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.331+39C>G		intron	N/A	NP_000192.2	A0A384MEK5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ICAM1	ENST00000264832.8	TSL:1 MANE Select	c.331+39C>G	intron	N/A	ENSP00000264832.2	P05362
ICAM1	ENST00000902798.1		c.331+39C>G	intron	N/A	ENSP00000572857.1
ICAM1	ENST00000935832.1		c.67+3841C>G	intron	N/A	ENSP00000605891.1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70165

AN:

152086

Hom.:

17979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.693

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.443

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.447

GnomAD2 exomes

AF:

0.370

AC:

88549

AN:

239548

AF XY:

0.371

show subpopulations

Gnomad AFR exome

AF:

0.705

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.453

Gnomad EAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.413

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.400

AC:

578512

AN:

1446404

Hom.:

120632

Cov.:

AF XY:

0.399

AC XY:

286698

AN XY:

718476

show subpopulations

African (AFR)

AF:

0.709

AC:

23487

AN:

33122

American (AMR)

AF:

0.217

AC:

9565

AN:

44000

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

11739

AN:

25884

East Asian (EAS)

AF:

0.131

AC:

5179

AN:

39486

South Asian (SAS)

AF:

0.350

AC:

29929

AN:

85430

European-Finnish (FIN)

AF:

0.407

AC:

19846

AN:

48774

Middle Eastern (MID)

AF:

0.455

AC:

2469

AN:

5428

European-Non Finnish (NFE)

AF:

0.409

AC:

451772

AN:

1104526

Other (OTH)

AF:

0.410

AC:

24526

AN:

59754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

16204

32408

48611

64815

81019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13942

27884

41826

55768

69710

<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:

0.462

AC:

70249

AN:

152204

Hom.:

18012

Cov.:

AF XY:

0.457

AC XY:

34005

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.694

AC:

28825

AN:

41554

American (AMR)

AF:

0.307

AC:

4694

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

1539

AN:

3472

East Asian (EAS)

AF:

0.157

AC:

816

AN:

5184

South Asian (SAS)

AF:

0.331

AC:

1595

AN:

4826

European-Finnish (FIN)

AF:

0.417

AC:

4418

AN:

10588

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27147

AN:

67984

Other (OTH)

AF:

0.449

AC:

948

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1793

3586

5378

7171

8964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.339

Hom.:

1423

Bravo

AF:

0.464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.82

(source)

DANN

Benign

0.46

PhyloP100

-0.37

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over