19-10286562-C-T

Position:

• chr19-10286562-C-T

Variant summary

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

The ENST00000264832.8(ICAM1):​c.*1275C>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 0.284 in 166,128 control chromosomes in the GnomAD database, including 7,229 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 0.29 (6760 hom., cov: 29)
  • Exomes 𝑓: 0.22 (469 hom.)
• Consequence: ICAM1 ENST00000264832.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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]

ICAM4-AS1 (HGNC:55990): (ICAM4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICAM1	NM_000201.3	c.*1275C>T		3_prime_UTR_variant	7/7	ENST00000264832.8	NP_000192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8	c.*1275C>T		3_prime_UTR_variant	7/7	1	NM_000201.3	ENSP00000264832	P1
ICAM4-AS1	ENST00000589379.1	n.2458G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 43905 AN: 151072 Hom.: 6751 Cov.: 29

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.220 AC: 3279 AN: 14938 Hom.: 469 Cov.: 0 AF XY: 0.222 AC XY: 1673 AN XY: 7532

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.0638

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.291 AC: 43957 AN: 151190 Hom.: 6760 Cov.: 29 AF XY: 0.286 AC XY: 21081 AN XY: 73782

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.292

Alfa AF: 0.279 Hom.: 8419

Bravo AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs281437; hg19: chr19-10397238;