19-10290422-G-C

Position:

• chr19-10290422-G-C

Variant summary

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

The NM_003259.4(ICAM5):​c.82+297G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 368,464 control chromosomes in the GnomAD database, including 30,073 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 (11066 hom., cov: 33)
  • Exomes 𝑓: 0.41 (19007 hom.)
• Consequence: ICAM5 NM_003259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICAM5	NM_003259.4	c.82+297G>C		intron_variant		ENST00000221980.5	NP_003250.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICAM5	ENST00000221980.5	c.82+297G>C		intron_variant		1	NM_003259.4	ENSP00000221980.3
ICAM5	ENST00000588912.1	n.430G>C		non_coding_transcript_exon_variant	1/1	6
ICAM5	ENST00000586004.1	n.102+297G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53986 AN: 152006 Hom.: 11067 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.411 AC: 88893 AN: 216340 Hom.: 19007 Cov.: 0 AF XY: 0.415 AC XY: 46164 AN XY: 111312

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.355 AC: 53989 AN: 152124 Hom.: 11066 Cov.: 33 AF XY: 0.356 AC XY: 26495 AN XY: 74372

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.408

Alfa AF: 0.261 Hom.: 671

Bravo AF: 0.356

Asia WGS AF: 0.357 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.1
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2075741; hg19: chr19-10401098;