Variant 20-34470149-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_031483.7(ITCH):c.1497+29G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,545,090 control chromosomes in the GnomAD database, including 191,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 18400 hom., cov: 31)

Exomes 𝑓: 0.49 ( 173303 hom. )

Consequence

ITCH
NM_031483.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.491

Variant links:

Genes affected

ITCH (HGNC:13890): (itchy E3 ubiquitin protein ligase) This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses. Mutations in this gene are a cause of syndromic multisystem autoimmune disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

ITCH links:

ENSG00000289720 (HGNC:):

ENSG00000289720 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 20-34470149-G-C is Benign according to our data. Variant chr20-34470149-G-C is described in ClinVar as [Benign]. Clinvar id is 2628157.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITCH	NM_031483.7 linkuse as main transcript	c.1497+29G>C		intron_variant		ENST00000374864.10	NP_113671.3	Q96J02-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITCH	ENST00000374864.10 linkuse as main transcript	c.1497+29G>C		intron_variant		1	NM_031483.7	ENSP00000363998.4		Q96J02-2
ENSG00000289720	ENST00000696979.1 linkuse as main transcript	n.1497+29G>C		intron_variant				ENSP00000513014.1

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

74189

AN:

149080

Hom.:

18376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.599

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.496

GnomAD3 exomes

AF:

0.477

AC:

119834

AN:

251436

Hom.:

30003

AF XY:

0.485

AC XY:

65975

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.495

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.601

Gnomad EAS exome

AF:

0.408

Gnomad SAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.586

Gnomad NFE exome

AF:

0.516

Gnomad OTH exome

AF:

0.506

GnomAD4 exome

AF:

0.494

AC:

689318

AN:

1395888

Hom.:

173303

Cov.:

AF XY:

0.496

AC XY:

346134

AN XY:

698374

show subpopulations

Gnomad4 AFR exome

AF:

0.496

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.606

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.584

Gnomad4 NFE exome

AF:

0.501

Gnomad4 OTH exome

AF:

0.501

GnomAD4 genome

AF:

0.498

AC:

74252

AN:

149202

Hom.:

18400

Cov.:

AF XY:

0.501

AC XY:

36477

AN XY:

72844

show subpopulations

Gnomad4 AFR

AF:

0.496

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.599

Gnomad4 NFE

AF:

0.513

Gnomad4 OTH

AF:

0.498

Alfa

AF:

0.523

Hom.:

3872

Bravo

AF:

0.472

Asia WGS

AF:

0.437

AC:

1521

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.4

DANN

Benign

0.61

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

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