19-10283549-C-G

Variant names:

• chr19-10283549-C-G
• rs768846633
• NM_000201.3:c.400C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000201.3(ICAM1):​c.400C>G​(p.Arg134Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R134C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ICAM1 NM_000201.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

Genes affected

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3	c.400C>G	p.Arg134Gly	missense_variant	Exon 3 of 7	ENST00000264832.8	NP_000192.2
LIMASI	XR_007067137.1	n.-99G>C		upstream_gene_variant
LIMASI	XR_007067138.1	n.-99G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8	c.400C>G	p.Arg134Gly	missense_variant	Exon 3 of 7	1	NM_000201.3	ENSP00000264832.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0069	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.029	D
Polyphen		0.98	D
Vest4		0.21
MutPred		0.51		Gain of ubiquitination at K129 (P = 0.05);
MVP		0.72
MPC		0.46
ClinPred		0.79	D
GERP RS		-8.0
Varity_R		0.40
gMVP		0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs768846633; hg19: chr19-10394225;