chr19-10286727-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000589379.1(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 ENST00000589379.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 78 publications found

Genes affected

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

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

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

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.

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	ENST00000380770.5	c.-286C>T		upstream_gene_variant		1	NM_001544.5	ENSP00000370147.2
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

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

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

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.59
PhyloP100		-0.30
PromoterAI		0.017	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3093030; hg19: chr19-10397403;