rs2278442

Positions:

• chr19-10334150-G-A
• chr19-10334150-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICAM3	NM_002162.5	c.1441+10C>T		intron_variant		ENST00000160262.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM3	ENST00000160262.10	c.1441+10C>T		intron_variant		1	NM_002162.5	P1
	ENST00000612689.1	n.715G>A		non_coding_transcript_exon_variant	1/1

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

GnomAD3 exomes AF: 0.670 AC: 167690 AN: 250138 Hom.: 56762 AF XY: 0.669 AC XY: 90520 AN XY: 135314

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 SAS 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

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.754

Gnomad4 SAS exome AF: 0.711

Gnomad4 FIN exome AF: 0.590

Gnomad4 NFE exome AF: 0.646

Gnomad4 OTH exome AF: 0.660

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

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.669

Alfa AF: 0.652 Hom.: 36599

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

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: rs2278442; hg19: chr19-10444826; COSMIC: COSV50329498; COSMIC: COSV50329498;