rs2230399

Variant names:

• chr19-10333927-C-G
• rs2230399
• NM_002162.5:c.1574G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-10333927-C-G
• chr19-10333927-C-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.1574G>C​(p.Ser525Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 1,613,934 control chromosomes in the GnomAD database, including 7,305 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1189 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6116 hom.)
• Consequence: ICAM3 NM_002162.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 29 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 (MetaRNN=0.0035166442).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM3	NM_002162.5	c.1574G>C	p.Ser525Thr	missense_variant	Exon 7 of 7	ENST00000160262.10	NP_002153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM3	ENST00000160262.10	c.1574G>C	p.Ser525Thr	missense_variant	Exon 7 of 7	1	NM_002162.5	ENSP00000160262.3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16713 AN: 152022 Hom.: 1177 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0755

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.0751 AC: 18873 AN: 251468 AF XY: 0.0743

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.0390

Gnomad ASJ exome AF: 0.0397

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.0799

Gnomad NFE exome AF: 0.0815

Gnomad OTH exome AF: 0.0655

GnomAD4 exome AF: 0.0859 AC: 125635 AN: 1461794 Hom.: 6116 Cov.: 34 AF XY: 0.0850 AC XY: 61811 AN XY: 727192

African (AFR) AF: 0.215 AC: 7204 AN: 33474

American (AMR) AF: 0.0422 AC: 1886 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 1078 AN: 26136

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.0781 AC: 6740 AN: 86258

European-Finnish (FIN) AF: 0.0791 AC: 4225 AN: 53406

Middle Eastern (MID) AF: 0.0678 AC: 391 AN: 5768

European-Non Finnish (NFE) AF: 0.0890 AC: 98971 AN: 1111936

Other (OTH) AF: 0.0848 AC: 5120 AN: 60392

GnomAD4 genome AF: 0.110 AC: 16760 AN: 152140 Hom.: 1189 Cov.: 32 AF XY: 0.108 AC XY: 8068 AN XY: 74392

African (AFR) AF: 0.205 AC: 8515 AN: 41472

American (AMR) AF: 0.0617 AC: 944 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.0753 AC: 363 AN: 4818

European-Finnish (FIN) AF: 0.0782 AC: 828 AN: 10594

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0840 AC: 5714 AN: 68000

Other (OTH) AF: 0.100 AC: 212 AN: 2112

Alfa AF: 0.0810 Hom.: 472

Bravo AF: 0.113

TwinsUK AF: 0.0968 AC: 359

ALSPAC AF: 0.0859 AC: 331

ESP6500AA AF: 0.200 AC: 880

ESP6500EA AF: 0.0844 AC: 726

ExAC AF: 0.0789 AC: 9579

Asia WGS AF: 0.0480 AC: 166 AN: 3478

EpiCase AF: 0.0773

EpiControl AF: 0.0807

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.86
DEOGEN2	Benign	0.047	T;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.38	T;T;T
MetaRNN	Benign	0.0035	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L;.;.
PhyloP100		-0.22
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.041
Sift	Benign	0.21	T;.;.
Sift4G	Benign	0.14	T;T;T
Polyphen		0.68	P;.;.
Vest4		0.049
MPC		0.38
ClinPred		0.0049	T
GERP RS		0.96
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.24
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: rs2230399; hg19: chr19-10444603; COSMIC: COSV50328770; COSMIC: COSV50328770;