Variant 5-5441109-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015325.3(ICE1):c.198-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 1,499,650 control chromosomes in the GnomAD database, including 75 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 66 hom. )

Consequence

ICE1
NM_015325.3 splice_region, intron

Scores

Splicing: ADA: 0.000007971

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.135

Variant links:

Genes affected

ICE1 (HGNC:29154): (interactor of little elongation complex ELL subunit 1) Enables protein-macromolecule adaptor activity. Involved in several processes, including positive regulation of intracellular protein transport; positive regulation of transcription by RNA polymerase III; and snRNA transcription. Located in Cajal body; histone locus body; and transcriptionally active chromatin. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ICE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 5-5441109-T-C is Benign according to our data. Variant chr5-5441109-T-C is described in ClinVar as [Benign]. Clinvar id is 771708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ICE1	NM_015325.3 linkuse as main transcript	c.198-3T>C	splice_region_variant, intron_variant	ENST00000296564.9	NP_056140.1	Q9Y2F5
ICE1	XM_011513999.3 linkuse as main transcript	c.198-3T>C	splice_region_variant, intron_variant		XP_011512301.1
ICE1	XM_047417046.1 linkuse as main transcript	c.198-3T>C	splice_region_variant, intron_variant		XP_047273002.1
ICE1	XM_047417047.1 linkuse as main transcript	c.198-3T>C	splice_region_variant, intron_variant		XP_047273003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICE1	ENST00000296564.9 linkuse as main transcript	c.198-3T>C		splice_region_variant, intron_variant		1	NM_015325.3	ENSP00000296564.7		Q9Y2F5
ICE1	ENST00000512608.5 linkuse as main transcript	c.-34-3T>C		splice_region_variant, intron_variant		4		ENSP00000485617.1		A0A096LPH9

Frequencies

GnomAD3 genomes

AF:

0.00614

AC:

935

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00970

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00575

AC:

933

AN:

162226

Hom.:

AF XY:

0.00543

AC XY:

464

AN XY:

85518

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00659

Gnomad ASJ exome

AF:

0.00445

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000919

Gnomad FIN exome

AF:

0.00404

Gnomad NFE exome

AF:

0.00934

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00792

AC:

10667

AN:

1347364

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

5190

AN XY:

668364

show subpopulations

Gnomad4 AFR exome

AF:

0.00153

Gnomad4 AMR exome

AF:

0.00668

Gnomad4 ASJ exome

AF:

0.00359

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00150

Gnomad4 FIN exome

AF:

0.00352

Gnomad4 NFE exome

AF:

0.00930

Gnomad4 OTH exome

AF:

0.00679

GnomAD4 genome

AF:

0.00614

AC:

935

AN:

152286

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

421

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.00811

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00970

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00779

Hom.:

Bravo

AF:

0.00660

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.6

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000080

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.030

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