dbSNP rs3093030: ICAM4-AS1:n.2293G>A (chr19-10286727-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 NR_186335.1(ICAM4-AS1):n.2293G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 363,998 control chromosomes in the GnomAD database, including 29,481 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 0.34 ( 10809 hom., cov: 31)

Exomes 𝑓: 0.41 ( 18672 hom. )

Consequence

ICAM4-AS1
NR_186335.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.301

Publications

78 publications found

Variant links:

Genes affected

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:

ICAM4 (HGNC:5347): (intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)) This gene encodes the Landsteiner-Wiener (LW) blood group antigen(s) that belongs to the immunoglobulin (Ig) superfamily, and that shares similarity with the intercellular adhesion molecule (ICAM) protein family. This ICAM protein contains 2 Ig-like C2-type domains and binds to the leukocyte adhesion LFA-1 protein. The molecular basis of the LW(A)/LW(B) blood group antigens is a single aa variation at position 100; Gln-100=LW(A) and Arg-100=LW(B). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ICAM4 links:

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:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_186335.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ICAM4-AS1	NR_186335.1		n.2293G>A	non_coding_transcript_exon	Exon 1 of 1
ICAM4	NM_001544.5	MANE Select	c.-286C>T	upstream_gene	N/A	NP_001535.1	Q14773-1
ICAM1	NM_000201.3	MANE Select	c.*1440C>T	downstream_gene	N/A	NP_000192.2	A0A384MEK5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ICAM4-AS1	ENST00000589379.1	TSL:6	n.2293G>A	non_coding_transcript_exon	Exon 1 of 1
LIMASI	ENST00000715961.1		n.395+3692G>A	intron	N/A
ICAM4-AS1	ENST00000724881.1		n.380-788G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52273

AN:

151886

Hom.:

10811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.398

GnomAD4 exome

AF:

0.412

AC:

87290

AN:

211994

Hom.:

18672

Cov.:

AF XY:

0.416

AC XY:

44624

AN XY:

107258

show subpopulations

African (AFR)

AF:

0.107

AC:

697

AN:

6492

American (AMR)

AF:

0.524

AC:

3332

AN:

6356

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

3659

AN:

8172

East Asian (EAS)

AF:

0.304

AC:

5899

AN:

19430

South Asian (SAS)

AF:

0.475

AC:

1663

AN:

3498

European-Finnish (FIN)

AF:

0.417

AC:

6783

AN:

16260

Middle Eastern (MID)

AF:

0.421

AC:

467

AN:

1110

European-Non Finnish (NFE)

AF:

0.432

AC:

58995

AN:

136410

Other (OTH)

AF:

0.406

AC:

5795

AN:

14266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2368

4736

7104

9472

11840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<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:

0.344

AC:

52267

AN:

152004

Hom.:

10809

Cov.:

AF XY:

0.347

AC XY:

25751

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.107

AC:

4440

AN:

41486

American (AMR)

AF:

0.493

AC:

7532

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

1588

AN:

3462

East Asian (EAS)

AF:

0.237

AC:

1225

AN:

5172

South Asian (SAS)

AF:

0.460

AC:

2220

AN:

4822

European-Finnish (FIN)

AF:

0.418

AC:

4410

AN:

10556

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29377

AN:

67926

Other (OTH)

AF:

0.398

AC:

839

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1588

3176

4764

6352

7940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.407

Hom.:

57667

Bravo

AF:

0.342

Asia WGS

AF:

0.355

AC:

1237

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.5

(source)

DANN

Benign

0.59

PhyloP100

-0.30

PromoterAI

0.017

Neutral

(source)

Splicing

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