19-10285660-C-T

Position:

• chr19-10285660-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000201.3(ICAM1):​c.*373C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 209,964 control chromosomes in the GnomAD database, including 1,402 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 0.097 (954 hom., cov: 32)
  • Exomes 𝑓: 0.11 (448 hom.)
• Consequence: ICAM1 NM_000201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

Genes affected

ICAM1 (HGNC:5344): (intercellular adhesion molecule 1) This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by Rhinovirus as a receptor. [provided by RefSeq, Jul 2008]

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 (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICAM1	NM_000201.3	c.*373C>T		3_prime_UTR_variant	7/7	ENST00000264832.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM1	ENST00000264832.8	c.*373C>T		3_prime_UTR_variant	7/7	1	NM_000201.3	P1

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14805 AN: 152092 Hom.: 955 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.114 AC: 6571 AN: 57754 Hom.: 448 Cov.: 0 AF XY: 0.114 AC XY: 3455 AN XY: 30182

Gnomad4 AFR exome AF: 0.0237

Gnomad4 AMR exome AF: 0.0743

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0333

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0972 AC: 14802 AN: 152210 Hom.: 954 Cov.: 32 AF XY: 0.0968 AC XY: 7205 AN XY: 74426

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0742

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0469

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.108

Alfa AF: 0.133 Hom.: 1926

Bravo AF: 0.0884

Asia WGS AF: 0.0910 AC: 317 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	1.9
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3093032; hg19: chr19-10396336;