19-10338716-A-G

Variant names:

• chr19-10338716-A-G
• rs2304240
• NM_002162.5:c.309T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002162.5(ICAM3):​c.309T>C​(p.Ser103Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 1,613,748 control chromosomes in the GnomAD database, including 558,442 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 0.85 (54659 hom., cov: 33)
  • Exomes 𝑓: 0.83 (503783 hom.)
• Consequence: ICAM3 NM_002162.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.174 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM3	NM_002162.5	c.309T>C	p.Ser103Ser	synonymous_variant	Exon 2 of 7	ENST00000160262.10	NP_002153.2
ICAM3	NM_001320606.2	c.78T>C	p.Ser26Ser	synonymous_variant	Exon 2 of 7		NP_001307535.1
ICAM3	NM_001320605.2	c.309T>C	p.Ser103Ser	synonymous_variant	Exon 2 of 6		NP_001307534.1
ICAM3	NM_001320608.2	c.-792T>C		5_prime_UTR_variant	Exon 2 of 6		NP_001307537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM3	ENST00000160262.10	c.309T>C	p.Ser103Ser	synonymous_variant	Exon 2 of 7	1	NM_002162.5	ENSP00000160262.3

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128576 AN: 152102 Hom.: 54611 Cov.: 33

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.857

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.831

GnomAD3 exomes AF: 0.808 AC: 202895 AN: 251214 Hom.: 83082 AF XY: 0.812 AC XY: 110253 AN XY: 135826

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.864

Gnomad EAS exome AF: 0.836

Gnomad SAS exome AF: 0.794

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.839

Gnomad OTH exome AF: 0.814

GnomAD4 exome AF: 0.829 AC: 1211204 AN: 1461528 Hom.: 503783 Cov.: 51 AF XY: 0.828 AC XY: 601973 AN XY: 727088

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.860

Gnomad4 EAS exome AF: 0.779

Gnomad4 SAS exome AF: 0.792

Gnomad4 FIN exome AF: 0.847

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.837

GnomAD4 genome AF: 0.845 AC: 128676 AN: 152220 Hom.: 54659 Cov.: 33 AF XY: 0.842 AC XY: 62618 AN XY: 74410

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.828

Alfa AF: 0.836 Hom.: 126774

Bravo AF: 0.839

Asia WGS AF: 0.796 AC: 2764 AN: 3478

EpiCase AF: 0.836

EpiControl AF: 0.836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.43

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: rs2304240; hg19: chr19-10449392;