dbSNP rs11575074: ICAM5:c.82+319G>A (chr19-10290444-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003259.4(ICAM5):c.82+319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 310,242 control chromosomes in the GnomAD database, including 562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.061 ( 336 hom., cov: 33)

Exomes 𝑓: 0.052 ( 226 hom. )

Consequence

ICAM5
NM_003259.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.758

Publications

13 publications found

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]

ICAM5 links:

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

LIMASI links:

ENSG00000294616 (HGNC:):

ENSG00000294616 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM5	NM_003259.4 link	c.82+319G>A		intron_variant	Intron 1 of 10	ENST00000221980.5	NP_003250.3	Q9UMF0Q8N6I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM5	ENST00000221980.5 link	c.82+319G>A		intron_variant	Intron 1 of 10	1	NM_003259.4	ENSP00000221980.3		Q9UMF0

Frequencies

GnomAD3 genomes

AF:

0.0613

AC:

9322

AN:

152132

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0564

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.0454

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0319

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0538

Gnomad OTH

AF:

0.0654

GnomAD4 exome

AF:

0.0521

AC:

8233

AN:

157992

Hom.:

226

Cov.:

AF XY:

0.0524

AC XY:

4191

AN XY:

79960

show subpopulations

African (AFR)

AF:

0.0791

AC:

376

AN:

4756

American (AMR)

AF:

0.0490

AC:

298

AN:

6080

Ashkenazi Jewish (ASJ)

AF:

0.0359

AC:

222

AN:

6176

East Asian (EAS)

AF:

0.0301

AC:

399

AN:

13254

South Asian (SAS)

AF:

0.106

AC:

557

AN:

5266

European-Finnish (FIN)

AF:

0.0348

AC:

369

AN:

10614

Middle Eastern (MID)

AF:

0.0711

AC:

AN:

830

European-Non Finnish (NFE)

AF:

0.0531

AC:

5332

AN:

100342

Other (OTH)

AF:

0.0582

AC:

621

AN:

10674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

379

759

1138

1518

1897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.0614

AC:

9343

AN:

152250

Hom.:

336

Cov.:

AF XY:

0.0608

AC XY:

4525

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0826

AC:

3430

AN:

41540

American (AMR)

AF:

0.0567

AC:

867

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

126

AN:

3472

East Asian (EAS)

AF:

0.0451

AC:

234

AN:

5184

South Asian (SAS)

AF:

0.108

AC:

520

AN:

4810

European-Finnish (FIN)

AF:

0.0319

AC:

338

AN:

10610

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0538

AC:

3659

AN:

68012

Other (OTH)

AF:

0.0652

AC:

138

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

449

899

1348

1798

2247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0563

Hom.:

Bravo

AF:

0.0619

Asia WGS

AF:

0.0800

AC:

279

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.76

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over