19-10290444-G-A

Position:

• chr19-10290444-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

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=-0.81).
• 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/exons	MANE	UniProt
ICAM5	NM_003259.4	c.82+319G>A		intron_variant		ENST00000221980.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM5	ENST00000221980.5	c.82+319G>A		intron_variant		1	NM_003259.4	P1
ICAM5	ENST00000588912.1	n.452G>A		non_coding_transcript_exon_variant	1/1
ICAM5	ENST00000586004.1	n.102+319G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9322 AN: 152132 Hom.: 334 Cov.: 33

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.: 0 AF XY: 0.0524 AC XY: 4191 AN XY: 79960

Gnomad4 AFR exome AF: 0.0791

Gnomad4 AMR exome AF: 0.0490

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.0301

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0348

Gnomad4 NFE exome AF: 0.0531

Gnomad4 OTH exome AF: 0.0582

GnomAD4 genome AF: 0.0614 AC: 9343 AN: 152250 Hom.: 336 Cov.: 33 AF XY: 0.0608 AC XY: 4525 AN XY: 74432

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.0451

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0319

Gnomad4 NFE AF: 0.0538

Gnomad4 OTH AF: 0.0652

Alfa AF: 0.0550 Hom.: 48

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	15
DANN	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs11575074; hg19: chr19-10401120;