rs1056538

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003259.4(ICAM5):​c.901G>A​(p.Val301Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,612,270 control chromosomes in the GnomAD database, including 117,960 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.31 ( 8971 hom., cov: 33)
Exomes 𝑓: 0.38 ( 108989 hom. )

Consequence

ICAM5
NM_003259.4 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.246
Variant links:
Genes affected
ICAM5 (HGNC:5348): (intercellular adhesion molecule 5) 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 expressed on the surface of telencephalic neurons and displays two types of adhesion activity, homophilic binding between neurons and heterophilic binding between neurons and leukocytes. It may be a critical component in neuron-microglial cell interactions in the course of normal development or as part of neurodegenerative diseases. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=2.8416514E-4).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ICAM5NM_003259.4 linkuse as main transcriptc.901G>A p.Val301Ile missense_variant 4/11 ENST00000221980.5 NP_003250.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ICAM5ENST00000221980.5 linkuse as main transcriptc.901G>A p.Val301Ile missense_variant 4/111 NM_003259.4 ENSP00000221980 P1
ICAM5ENST00000586480.1 linkuse as main transcriptc.526G>A p.Val176Ile missense_variant 2/91 ENSP00000516504

Frequencies

GnomAD3 genomes
AF:
0.312
AC:
47491
AN:
152134
Hom.:
8973
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0962
Gnomad AMI
AF:
0.560
Gnomad AMR
AF:
0.463
Gnomad ASJ
AF:
0.389
Gnomad EAS
AF:
0.242
Gnomad SAS
AF:
0.399
Gnomad FIN
AF:
0.358
Gnomad MID
AF:
0.358
Gnomad NFE
AF:
0.393
Gnomad OTH
AF:
0.360
GnomAD3 exomes
AF:
0.385
AC:
95628
AN:
248350
Hom.:
20093
AF XY:
0.388
AC XY:
52238
AN XY:
134788
show subpopulations
Gnomad AFR exome
AF:
0.0915
Gnomad AMR exome
AF:
0.582
Gnomad ASJ exome
AF:
0.384
Gnomad EAS exome
AF:
0.229
Gnomad SAS exome
AF:
0.403
Gnomad FIN exome
AF:
0.363
Gnomad NFE exome
AF:
0.390
Gnomad OTH exome
AF:
0.400
GnomAD4 exome
AF:
0.381
AC:
555902
AN:
1460018
Hom.:
108989
Cov.:
48
AF XY:
0.382
AC XY:
277140
AN XY:
726328
show subpopulations
Gnomad4 AFR exome
AF:
0.0822
Gnomad4 AMR exome
AF:
0.566
Gnomad4 ASJ exome
AF:
0.383
Gnomad4 EAS exome
AF:
0.284
Gnomad4 SAS exome
AF:
0.403
Gnomad4 FIN exome
AF:
0.364
Gnomad4 NFE exome
AF:
0.385
Gnomad4 OTH exome
AF:
0.369
GnomAD4 genome
AF:
0.312
AC:
47486
AN:
152252
Hom.:
8971
Cov.:
33
AF XY:
0.313
AC XY:
23319
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0959
Gnomad4 AMR
AF:
0.463
Gnomad4 ASJ
AF:
0.389
Gnomad4 EAS
AF:
0.242
Gnomad4 SAS
AF:
0.400
Gnomad4 FIN
AF:
0.358
Gnomad4 NFE
AF:
0.393
Gnomad4 OTH
AF:
0.359
Alfa
AF:
0.352
Hom.:
4342
Bravo
AF:
0.312
TwinsUK
AF:
0.375
AC:
1389
ALSPAC
AF:
0.375
AC:
1445
ESP6500AA
AF:
0.0990
AC:
436
ESP6500EA
AF:
0.389
AC:
3345
ExAC
AF:
0.373
AC:
45233
Asia WGS
AF:
0.335
AC:
1171
AN:
3478
EpiCase
AF:
0.401
EpiControl
AF:
0.401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.77
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.066
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.022
T
MetaRNN
Benign
0.00028
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.66
N
REVEL
Benign
0.035
Sift
Benign
0.20
T
Sift4G
Benign
0.12
T
Polyphen
0.0060
B
Vest4
0.019
ClinPred
0.0055
T
GERP RS
3.3
Varity_R
0.13
gMVP
0.16

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1056538; hg19: chr19-10402938; COSMIC: COSV55746359; COSMIC: COSV55746359; API