chr19-10334150-G-A

Variant names:

• chr19-10334150-G-A
• rs2278442
• NM_002162.5:c.1441+10C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002162.5(ICAM3):​c.1441+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,611,020 control chromosomes in the GnomAD database, including 346,747 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 0.65 (31891 hom., cov: 27)
  • Exomes 𝑓: 0.66 (314856 hom.)
• Consequence: ICAM3 NM_002162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 48 publications found

Genes affected

ICAM3 (HGNC:5346): (intercellular adhesion molecule 3) 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 constitutively and abundantly expressed by all leucocytes and may be the most important ligand for LFA-1 in the initiation of the immune response. It functions not only as an adhesion molecule, but also as a potent signalling molecule. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ENSG00000274425 (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 (AMR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM3	NM_002162.5	c.1441+10C>T		intron_variant	Intron 6 of 6	ENST00000160262.10	NP_002153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM3	ENST00000160262.10	c.1441+10C>T		intron_variant	Intron 6 of 6	1	NM_002162.5	ENSP00000160262.3

Frequencies

GnomAD3 genomes AF: 0.647 AC: 97847 AN: 151200 Hom.: 31859 Cov.: 27

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.672

GnomAD2 exomes AF: 0.670 AC: 167690 AN: 250138 AF XY: 0.669

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.799

Gnomad ASJ exome AF: 0.638

Gnomad EAS exome AF: 0.706

Gnomad FIN exome AF: 0.586

Gnomad NFE exome AF: 0.642

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.655 AC: 956493 AN: 1459702 Hom.: 314856 Cov.: 46 AF XY: 0.656 AC XY: 476269 AN XY: 725782

African (AFR) AF: 0.619 AC: 20714 AN: 33454

American (AMR) AF: 0.795 AC: 35507 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 16799 AN: 26112

East Asian (EAS) AF: 0.754 AC: 29894 AN: 39642

South Asian (SAS) AF: 0.711 AC: 61272 AN: 86222

European-Finnish (FIN) AF: 0.590 AC: 31426 AN: 53268

Middle Eastern (MID) AF: 0.685 AC: 3943 AN: 5758

European-Non Finnish (NFE) AF: 0.646 AC: 717114 AN: 1110252

Other (OTH) AF: 0.660 AC: 39824 AN: 60314

GnomAD4 genome AF: 0.647 AC: 97932 AN: 151318 Hom.: 31891 Cov.: 27 AF XY: 0.647 AC XY: 47807 AN XY: 73888

African (AFR) AF: 0.622 AC: 25623 AN: 41206

American (AMR) AF: 0.725 AC: 11010 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2282 AN: 3460

East Asian (EAS) AF: 0.719 AC: 3676 AN: 5114

South Asian (SAS) AF: 0.704 AC: 3362 AN: 4776

European-Finnish (FIN) AF: 0.596 AC: 6244 AN: 10474

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43531 AN: 67804

Other (OTH) AF: 0.669 AC: 1403 AN: 2098

Alfa AF: 0.651 Hom.: 51616

Bravo AF: 0.657

Asia WGS AF: 0.709 AC: 2468 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	0.93
DANN	Benign	0.77
PhyloP100		-1.2
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: rs2278442; hg19: chr19-10444826; COSMIC: COSV50329498; COSMIC: COSV50329498;