19-10287757-C-T

Variant names:

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

Variant summary

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

The NM_001544.5(ICAM4):​c.616C>T​(p.Gln206*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ICAM4 NM_001544.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Gln206*	stop_gained	Exon 2 of 3	NP_001535.1	Q14773-1
	ICAM4	NM_001039132.3		c.539C>T	p.Ala180Val	missense	Exon 2 of 3	NP_001034221.1	U5U6P8
	ICAM4-AS1	NR_186335.1		n.1263G>A		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>T	p.Gln206*	stop_gained	Exon 2 of 3	ENSP00000370147.2	Q14773-1
	ICAM4	ENST00000340992.4	TSL:1	c.539C>T	p.Ala180Val	missense	Exon 2 of 3	ENSP00000342114.3	Q14773-3
	ICAM4	ENST00000929145.1		c.646C>T	p.Gln216*	stop_gained	Exon 2 of 3	ENSP00000599204.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.19
MutPred		0.29		Gain of sheet (P = 0.0827)
MVP		0.19
MPC		1.0
ClinPred		0.96	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.23
Mutation Taster		=128/72	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; COSMIC: COSV108068141; COSMIC: COSV108068141;