19-10271151-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000201.3(ICAM1):c.-9A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,612,170 control chromosomes in the GnomAD database, including 1,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (997 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (908 hom.)
• Consequence: ICAM1 NM_000201.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.610

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]

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 19-10271151-A-C is Benign according to our data. Variant chr19-10271151-A-C is described in ClinVar as [Benign]. Clinvar id is 3056696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICAM1	NM_000201.3	c.-9A>C		5_prime_UTR_variant	1/7	ENST00000264832.8
LIMASI	XR_007067138.1	n.131-4357T>G		intron_variant, non_coding_transcript_variant
LIMASI	XR_007067137.1	n.131-4357T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM1	ENST00000264832.8	c.-9A>C		5_prime_UTR_variant	1/7	1	NM_000201.3	P1
LIMASI	ENST00000592893.1	n.142-10723T>G		intron_variant, non_coding_transcript_variant		3
ICAM1	ENST00000423829.2	c.-9A>C		5_prime_UTR_variant	1/5	2
ICAM1	ENST00000588645.1	c.-9A>C		5_prime_UTR_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9572 AN: 152100 Hom.: 995 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0531

GnomAD3 exomes AF: 0.0159 AC: 3922 AN: 246402 Hom.: 372 AF XY: 0.0116 AC XY: 1551 AN XY: 134016

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.00997

Gnomad ASJ exome AF: 0.00182

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000494

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000667

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00647 AC: 9447 AN: 1459952 Hom.: 908 Cov.: 30 AF XY: 0.00547 AC XY: 3973 AN XY: 726274

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.00127

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000523

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000392

Gnomad4 OTH exome AF: 0.0149

GnomAD4 genome AF: 0.0629 AC: 9582 AN: 152218 Hom.: 997 Cov.: 32 AF XY: 0.0610 AC XY: 4544 AN XY: 74434

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0525

Alfa AF: 0.0330 Hom.: 286

Bravo AF: 0.0724

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000831

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ICAM1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.0
Dann	Benign	0.40
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: rs5490; hg19: chr19-10381827;