ENST00000589261.5:n.252A>C

Variant names:

• chr19-10339075-T-G
• rs3176767
• ENST00000589261.5:n.252A>C

Variant summary

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

The ENST00000589261.5(ICAM3):​n.252A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 998,410 control chromosomes in the GnomAD database, including 22,640 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 0.20 (3229 hom., cov: 32)
  • Exomes 𝑓: 0.21 (19411 hom.)
• Consequence: ICAM3 ENST00000589261.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 25 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047955513).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM3	NM_002162.5	c.77-127A>C		intron_variant	Intron 1 of 6	ENST00000160262.10	NP_002153.2
ICAM3	NM_001320606.2	c.-282A>C		5_prime_UTR_variant	Exon 2 of 7		NP_001307535.1
ICAM3	NM_001320605.2	c.77-127A>C		intron_variant	Intron 1 of 5		NP_001307534.1
ICAM3	NM_001320608.2	c.-1024-127A>C		intron_variant	Intron 1 of 5		NP_001307537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM3	ENST00000160262.10	c.77-127A>C		intron_variant	Intron 1 of 6	1	NM_002162.5	ENSP00000160262.3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30752 AN: 151734 Hom.: 3231 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.192 AC: 19986 AN: 104130 AF XY: 0.194

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.209 AC: 177266 AN: 846558 Hom.: 19411 Cov.: 11 AF XY: 0.212 AC XY: 91468 AN XY: 430894

African (AFR) AF: 0.150 AC: 3040 AN: 20262

American (AMR) AF: 0.175 AC: 4559 AN: 26006

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 4097 AN: 17020

East Asian (EAS) AF: 0.130 AC: 4526 AN: 34744

South Asian (SAS) AF: 0.266 AC: 15422 AN: 57908

European-Finnish (FIN) AF: 0.202 AC: 6682 AN: 33098

Middle Eastern (MID) AF: 0.243 AC: 786 AN: 3230

European-Non Finnish (NFE) AF: 0.212 AC: 130024 AN: 614696

Other (OTH) AF: 0.205 AC: 8130 AN: 39594

GnomAD4 genome AF: 0.202 AC: 30746 AN: 151852 Hom.: 3229 Cov.: 32 AF XY: 0.201 AC XY: 14949 AN XY: 74212

African (AFR) AF: 0.160 AC: 6646 AN: 41416

American (AMR) AF: 0.179 AC: 2729 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3468

East Asian (EAS) AF: 0.119 AC: 615 AN: 5174

South Asian (SAS) AF: 0.256 AC: 1234 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2183 AN: 10536

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15683 AN: 67918

Other (OTH) AF: 0.222 AC: 468 AN: 2106

Alfa AF: 0.222 Hom.: 10247

Bravo AF: 0.198

TwinsUK AF: 0.217 AC: 805

ALSPAC AF: 0.236 AC: 908

ExAC AF: 0.144 AC: 16334

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.073
DANN	Benign	0.27
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0048	T
PhyloP100		-2.6
GERP RS		-6.2
Mutation Taster		=300/0	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: rs3176767; hg19: chr19-10449751;