19-10283648-G-T

Variant names:

• chr19-10283648-G-T
• rs769975581
• NM_000201.3:c.499G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000201.3(ICAM1):​c.499G>T​(p.Ala167Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.000018 (0 hom.)
• Consequence: ICAM1 NM_000201.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.668
• Publications: 0 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08515102).

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.499G>T	p.Ala167Ser	missense	Exon 3 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.499G>T	p.Ala167Ser	missense	Exon 3 of 7	ENSP00000264832.2	P05362
	ICAM1	ENST00000902798.1		c.499G>T	p.Ala167Ser	missense	Exon 3 of 6	ENSP00000572857.1
	ICAM1	ENST00000935832.1		c.235G>T	p.Ala79Ser	missense	Exon 2 of 6	ENSP00000605891.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000720 AC: 18 AN: 249916 AF XY: 0.0000814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461482 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 727030

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111870

Other (OTH) AF: 0.0000497 AC: 3 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000357 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

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	0.12
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.67
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.068
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.021	D
Polyphen		0.15	B
Vest4		0.15
MutPred		0.53		Gain of disorder (P = 0.0545)
MVP		0.75
MPC		0.38
ClinPred		0.17	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.25
Mutation Taster		=95/5	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: rs769975581; hg19: chr19-10394324;