rs885743

chr19-10295959-T-Achr19-10295959-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003259.4(ICAM5):c.2497+347T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,762 control chromosomes in the GnomAD database, including 10,928 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 0.35 (10928 hom., cov: 30)
• Consequence: ICAM5 NM_003259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICAM5	NM_003259.4	c.2497+347T>A		intron_variant		ENST00000221980.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM5	ENST00000221980.5	c.2497+347T>A		intron_variant		1	NM_003259.4	P1
ICAM5	ENST00000586480.1	c.2122+347T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53522 AN: 151644 Hom.: 10928 Cov.: 30

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.353 AC: 53528 AN: 151762 Hom.: 10928 Cov.: 30 AF XY: 0.353 AC XY: 26206 AN XY: 74150

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.405

Alfa AF: 0.388 Hom.: 1539

Bravo AF: 0.353

Asia WGS AF: 0.344 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.8
Dann	Benign	0.44
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		2.0

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

Other links and lift over

dbSNP: rs885743; hg19: chr19-10406635;