NM_000201.3:c.130G>T

Variant names:

• chr19-10274827-G-T
• rs771818150
• NM_000201.3:c.130G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000201.3(ICAM1):​c.130G>T​(p.Val44Leu) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. 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. V44M) 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: -2.88
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05859211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000201.3. 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
	ICAM1	NM_000201.3	MANE Select	c.130G>T	p.Val44Leu	missense	Exon 2 of 7	NP_000192.2	A0A384MEK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM1	ENST00000264832.8	TSL:1 MANE Select	c.130G>T	p.Val44Leu	missense	Exon 2 of 7	ENSP00000264832.2	P05362
	ICAM1	ENST00000902798.1		c.130G>T	p.Val44Leu	missense	Exon 2 of 6	ENSP00000572857.1
	ICAM1	ENST00000588645.1	TSL:2	c.130G>T	p.Val44Leu	missense	Exon 2 of 4	ENSP00000465680.1	K7EKL8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0010
DANN	Benign	0.21
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.44	N
PhyloP100		-2.9
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.12
MutPred		0.53		Loss of catalytic residue at V44 (P = 0.0241)
MVP		0.24
MPC		0.16
ClinPred		0.079	T
GERP RS		-7.2
Varity_R		0.22
gMVP		0.43
Mutation Taster		=87/13	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: rs771818150; hg19: chr19-10385503;