19-10290422-G-C

Variant names:

• chr19-10290422-G-C
• rs2075741
• NM_003259.4:c.82+297G>C

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+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
• Publications: 16 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=-0.86).
• 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 rank	MANE	Protein	UniProt
ICAM5	NM_003259.4	c.82+297G>C		intron_variant	Intron 1 of 10	ENST00000221980.5	NP_003250.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM5	ENST00000221980.5	c.82+297G>C		intron_variant	Intron 1 of 10	1	NM_003259.4	ENSP00000221980.3

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

African (AFR) AF: 0.144 AC: 840 AN: 5844

American (AMR) AF: 0.537 AC: 4176 AN: 7778

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 3478 AN: 7786

East Asian (EAS) AF: 0.312 AC: 5139 AN: 16496

South Asian (SAS) AF: 0.424 AC: 5633 AN: 13274

European-Finnish (FIN) AF: 0.410 AC: 6252 AN: 15262

Middle Eastern (MID) AF: 0.402 AC: 444 AN: 1104

European-Non Finnish (NFE) AF: 0.424 AC: 57198 AN: 134830

Other (OTH) AF: 0.410 AC: 5733 AN: 13966

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

African (AFR) AF: 0.145 AC: 6023 AN: 41532

American (AMR) AF: 0.500 AC: 7639 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1587 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1259 AN: 5164

South Asian (SAS) AF: 0.443 AC: 2135 AN: 4818

European-Finnish (FIN) AF: 0.417 AC: 4413 AN: 10586

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29440 AN: 67950

Other (OTH) AF: 0.408 AC: 862 AN: 2114

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
PhyloP100		-0.78
PromoterAI		-0.0019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075741; hg19: chr19-10401098;