19-10288699-T-G

Variant names:

• chr19-10288699-T-G
• rs281438
• ENST00000589379.1:n.321A>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 23 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]

ACMG classification

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: ENST00000589379.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	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
	ICAM4	NM_001039132.3		c.*515T>G		downstream_gene	N/A	NP_001034221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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.: 32

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.: 0 AF XY: 0.327 AC XY: 591 AN XY: 1810

African (AFR) AF: 0.875 AC: 7 AN: 8

American (AMR) AF: 0.251 AC: 90 AN: 358

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 7 AN: 20

East Asian (EAS) AF: 0.0676 AC: 5 AN: 74

South Asian (SAS) AF: 0.347 AC: 207 AN: 596

European-Finnish (FIN) AF: 0.306 AC: 11 AN: 36

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.345 AC: 657 AN: 1902

Other (OTH) AF: 0.296 AC: 29 AN: 98

GnomAD4 genome AF: 0.301 AC: 45675 AN: 151970 Hom.: 7364 Cov.: 32 AF XY: 0.296 AC XY: 21955 AN XY: 74274

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

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
DANN	Benign	0.49
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs281438; hg19: chr19-10399375;