rs11575074

Variant names:

• chr19-10290444-G-A
• rs11575074
• NM_003259.4:c.82+319G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

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

ENSG00000294616 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003259.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM5	NM_003259.4	MANE Select	c.82+319G>A		intron	N/A	NP_003250.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM5	ENST00000221980.5	TSL:1 MANE Select	c.82+319G>A		intron	N/A	ENSP00000221980.3
	ICAM5	ENST00000948402.1		c.82+319G>A		intron	N/A	ENSP00000618461.1
	ICAM5	ENST00000588912.1	TSL:6	n.452G>A		non_coding_transcript_exon	Exon 1 of 1

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

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: 59 AN: 830

European-Non Finnish (NFE) AF: 0.0531 AC: 5332 AN: 100342

Other (OTH) AF: 0.0582 AC: 621 AN: 10674

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

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: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3659 AN: 68012

Other (OTH) AF: 0.0652 AC: 138 AN: 2116

Alfa AF: 0.0563 Hom.: 95

Bravo AF: 0.0619

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		0.76
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11575074; hg19: chr19-10401120;