Genetic Variant NM_002162.5:c.917G>A (chr19-10335086-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002162.5(ICAM3):c.917G>A(p.Arg306Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000608 in 1,613,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

ICAM3
NM_002162.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.636

Publications

2 publications found

Variant links:

Genes affected

ICAM3 (HGNC:5346): (intercellular adhesion molecule 3) The protein encoded by this gene is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins, contain 2-9 immunoglobulin-like C2-type domains, and bind to the leukocyte adhesion LFA-1 protein. This protein is constitutively and abundantly expressed by all leucocytes and may be the most important ligand for LFA-1 in the initiation of the immune response. It functions not only as an adhesion molecule, but also as a potent signalling molecule. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ICAM3 links:

ENSG00000274425 (HGNC:):

ENSG00000274425 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009539574).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002162.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ICAM3	NM_002162.5	MANE Select	c.917G>A	p.Arg306Gln	missense	Exon 4 of 7	NP_002153.2	P32942
ICAM3	NM_001320606.2		c.686G>A	p.Arg229Gln	missense	Exon 4 of 7	NP_001307535.1
ICAM3	NM_001395374.1		c.332G>A	p.Arg111Gln	missense	Exon 2 of 5	NP_001382303.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ICAM3	ENST00000160262.10	TSL:1 MANE Select	c.917G>A	p.Arg306Gln	missense	Exon 4 of 7	ENSP00000160262.3	P32942
ICAM3	ENST00000589261.5	TSL:1	n.1219G>A		non_coding_transcript_exon	Exon 4 of 7
ICAM3	ENST00000912542.1		c.649+585G>A		intron	N/A	ENSP00000582601.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000204

AC:

AN:

250282

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.0000589

AC:

AN:

1460958

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

726712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.000805

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00127

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111620

Other (OTH)

AF:

0.0000663

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.000957

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.1

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.058

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.82

M_CAP

Benign

0.0094

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

PhyloP100

-0.64

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.79

REVEL

Benign

0.0050

Sift

Benign

0.45

Sift4G

Benign

0.23

Polyphen

0.41

Vest4

0.15

MutPred

0.39

Loss of sheet (P = 0.1158)

MVP

0.23

MPC

0.51

ClinPred

0.021

GERP RS

-1.8

PromoterAI

-0.064

Neutral

(source)

Varity_R

0.096

gMVP

0.23

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over