Genetic Variant NM_000201.3:c.331+39C>T (chr19-10275067-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000201.3(ICAM1):c.331+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00672 in 1,600,218 control chromosomes in the GnomAD database, including 47 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 0.0051 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 43 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3 link	c.331+39C>T	intron_variant	Intron 2 of 6	ENST00000264832.8	NP_000192.2	P05362A0A384MEK5
LIMASI	XR_007067137.1 link	n.130+8254G>A	intron_variant	Intron 1 of 3
LIMASI	XR_007067138.1 link	n.130+8254G>A	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8 link	c.331+39C>T		intron_variant	Intron 2 of 6	1	NM_000201.3	ENSP00000264832.2		P05362

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

782

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00834

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00544

AC:

1303

AN:

239548

AF XY:

0.00565

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000220

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.00924

Gnomad OTH exome

AF:

0.00422

GnomAD4 exome

AF:

0.00689

AC:

9976

AN:

1447954

Hom.:

Cov.:

AF XY:

0.00675

AC XY:

4852

AN XY:

719246

show subpopulations

African (AFR)

AF:

0.00109

AC:

AN:

33146

American (AMR)

AF:

0.00136

AC:

AN:

44016

Ashkenazi Jewish (ASJ)

AF:

0.000193

AC:

AN:

25906

East Asian (EAS)

AF:

0.000177

AC:

AN:

39508

South Asian (SAS)

AF:

0.000936

AC:

AN:

85468

European-Finnish (FIN)

AF:

0.0103

AC:

501

AN:

48842

Middle Eastern (MID)

AF:

0.000552

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

0.00814

AC:

8998

AN:

1105816

Other (OTH)

AF:

0.00478

AC:

286

AN:

59816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

479

957

1436

1914

2393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.00514

AC:

783

AN:

152264

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

385

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41570

American (AMR)

AF:

0.000916

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0117

AC:

124

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00834

AC:

567

AN:

68008

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00487

Hom.:

1423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.97

PhyloP100

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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