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 NR_186335.1(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
NR_186335.1 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.

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.321A>C	non_coding_transcript_exon	Exon 1 of 1
ICAM4	NM_001544.5	MANE Select	c.*595T>G	downstream_gene	N/A	NP_001535.1	Q14773-1
ICAM4	NM_001039132.3		c.*515T>G	downstream_gene	N/A	NP_001034221.1	U5U6P8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ICAM4-AS1	ENST00000589379.1	TSL:6	n.321A>C	non_coding_transcript_exon	Exon 1 of 1
LIMASI	ENST00000715961.1		n.395+1720A>C	intron	N/A
ICAM4-AS1	ENST00000724881.1		n.379+249A>C	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over