rs3093030

Variant names:

• chr19-10286727-C-T
• rs3093030
• ENST00000589379.1:n.2293G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

Genes affected

ICAM4-AS1 (HGNC:55990): (ICAM4 antisense RNA 1)

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]

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM4-AS1	NR_186335.1	n.2293G>A		non_coding_transcript_exon_variant	Exon 1 of 1
ICAM4	NM_001544.5	c.-286C>T		upstream_gene_variant		ENST00000380770.5	NP_001535.1
ICAM1	NM_000201.3	c.*1440C>T		downstream_gene_variant		ENST00000264832.8	NP_000192.2
ICAM4	NM_001039132.3	c.-286C>T		upstream_gene_variant			NP_001034221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM4-AS1	ENST00000589379.1	n.2293G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ICAM4	ENST00000380770.5	c.-286C>T		upstream_gene_variant		1	NM_001544.5	ENSP00000370147.2
ICAM4	ENST00000340992.4	c.-286C>T		upstream_gene_variant		1		ENSP00000342114.3
ICAM1	ENST00000264832.8	c.*1440C>T		downstream_gene_variant		1	NM_000201.3	ENSP00000264832.2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52273 AN: 151886 Hom.: 10811 Cov.: 31

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.: 2 AF XY: 0.416 AC XY: 44624 AN XY: 107258

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.344 AC: 52267 AN: 152004 Hom.: 10809 Cov.: 31 AF XY: 0.347 AC XY: 25751 AN XY: 74280

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.398

Alfa AF: 0.423 Hom.: 30373

Bravo AF: 0.342

Asia WGS AF: 0.355 AC: 1237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3093030; hg19: chr19-10397403;