rs1568297555

Variant names:

• chr19-10287757-C-A
• rs1568297555
• NM_001544.5:c.616C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-10287757-C-A
• chr19-10287757-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001544.5(ICAM4):​c.616C>A​(p.Gln206Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ICAM4 NM_001544.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19778666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001544.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM4	NM_001544.5	MANE Select	c.616C>A	p.Gln206Lys	missense	Exon 2 of 3	NP_001535.1	Q14773-1
	ICAM4	NM_001039132.3		c.539C>A	p.Ala180Glu	missense	Exon 2 of 3	NP_001034221.1	U5U6P8
	ICAM4-AS1	NR_186335.1		n.1263G>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM4	ENST00000380770.5	TSL:1 MANE Select	c.616C>A	p.Gln206Lys	missense	Exon 2 of 3	ENSP00000370147.2	Q14773-1
	ICAM4	ENST00000340992.4	TSL:1	c.539C>A	p.Ala180Glu	missense	Exon 2 of 3	ENSP00000342114.3	Q14773-3
	ICAM4	ENST00000929145.1		c.646C>A	p.Gln216Lys	missense	Exon 2 of 3	ENSP00000599204.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461576 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.88
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.067
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.29
MutPred		0.32		Loss of sheet (P = 0.0037)
MVP		0.12
MPC		1.3
ClinPred		0.87	D
GERP RS		2.6
Varity_R		0.078
gMVP		0.30
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1568297555; hg19: chr19-10398433;