Variant 19-10283477-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000201.3(ICAM1):c.332-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,541,652 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

ICAM1
NM_000201.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001800

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.38

Variant links:

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]

ICAM1 links:

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

LIMASI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-10283477-G-A is Benign according to our data. Variant chr19-10283477-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649290.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ICAM1	NM_000201.3 linkuse as main transcript	c.332-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000264832.8
LIMASI	XR_007067138.1 linkuse as main transcript		upstream_gene_variant
LIMASI	XR_007067137.1 linkuse as main transcript		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM1	ENST00000264832.8 linkuse as main transcript	c.332-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000201.3	P1
LIMASI	ENST00000592893.1 linkuse as main transcript	n.141+1491C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000604

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000486

AC:

AN:

197496

Hom.:

AF XY:

0.000476

AC XY:

AN XY:

105022

show subpopulations

Gnomad AFR exome

AF:

0.000385

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000983

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00106

AC:

1475

AN:

1389334

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

706

AN XY:

682832

show subpopulations

Gnomad4 AFR exome

AF:

0.000221

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.000454

GnomAD4 genome

AF:

0.000604

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.000431

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

ICAM1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.15

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over