dbSNP rs281438: ICAM4-AS1:n.321A>C (chr19-10288699-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000589379.1(ICAM4-AS1):n.321A>C 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 0.301 in 155,062 control chromosomes in the GnomAD database, including 7,530 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 0.30 ( 7364 hom., cov: 32)

Exomes 𝑓: 0.33 ( 166 hom. )

Consequence

ICAM4-AS1
ENST00000589379.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.161

Publications

23 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:

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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=-0.71).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ICAM4-AS1	NR_186335.1 link	n.321A>C	non_coding_transcript_exon_variant	Exon 1 of 1
ICAM4	NM_001544.5 link	c.*595T>G	downstream_gene_variant		ENST00000380770.5	NP_001535.1
ICAM4	NM_001039132.3 link	c.*515T>G	downstream_gene_variant			NP_001034221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM4	ENST00000380770.5 link	c.*595T>G		downstream_gene_variant		1	NM_001544.5	ENSP00000370147.2

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45611

AN:

151850

Hom.:

7347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.293

GnomAD4 exome

AF:

0.328

AC:

1013

AN:

3092

Hom.:

166

Cov.:

AF XY:

0.327

AC XY:

591

AN XY:

1810

show subpopulations

African (AFR)

AF:

0.875

AC:

AN:

American (AMR)

AF:

0.251

AC:

AN:

358

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

AN:

East Asian (EAS)

AF:

0.0676

AC:

AN:

South Asian (SAS)

AF:

0.347

AC:

207

AN:

596

European-Finnish (FIN)

AF:

0.306

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.345

AC:

657

AN:

1902

Other (OTH)

AF:

0.296

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.301

AC:

45675

AN:

151970

Hom.:

7364

Cov.:

AF XY:

0.296

AC XY:

21955

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.399

AC:

16527

AN:

41418

American (AMR)

AF:

0.219

AC:

3347

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

981

AN:

3464

East Asian (EAS)

AF:

0.102

AC:

528

AN:

5170

South Asian (SAS)

AF:

0.280

AC:

1347

AN:

4810

European-Finnish (FIN)

AF:

0.253

AC:

2671

AN:

10556

Middle Eastern (MID)

AF:

0.417

AC:

121

AN:

290

European-Non Finnish (NFE)

AF:

0.286

AC:

19424

AN:

67976

Other (OTH)

AF:

0.297

AC:

628

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1634

3267

4901

6534

8168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.293

Hom.:

1506

Bravo

AF:

0.301

Asia WGS

AF:

0.221

AC:

766

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.0

(source)

DANN

Benign

0.49

PhyloP100

-0.16

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over