Variant chr20-34449531-C-T 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.1210+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,193,640 control chromosomes in the GnomAD database, including 143,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.45 ( 15737 hom., cov: 31)

Exomes 𝑓: 0.49 ( 127295 hom. )

Consequence

ITCH
NM_031483.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01

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:

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=-0.9).

BP6

Variant 20-34449531-C-T is Benign according to our data. Variant chr20-34449531-C-T is described in ClinVar as [Benign]. Clinvar id is 2628156.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITCH	NM_031483.7 linkuse as main transcript	c.1210+51C>T		intron_variant		ENST00000374864.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITCH	ENST00000374864.10 linkuse as main transcript	c.1210+51C>T		intron_variant		1	NM_031483.7	P1	Q96J02-2

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67888

AN:

151720

Hom.:

15730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.457

GnomAD3 exomes

AF:

0.458

AC:

109681

AN:

239352

Hom.:

26412

AF XY:

0.468

AC XY:

60409

AN XY:

129050

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.595

Gnomad EAS exome

AF:

0.407

Gnomad SAS exome

AF:

0.446

Gnomad FIN exome

AF:

0.586

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.494

GnomAD4 exome

AF:

0.488

AC:

507880

AN:

1041802

Hom.:

127295

Cov.:

AF XY:

0.489

AC XY:

261955

AN XY:

535980

show subpopulations

Gnomad4 AFR exome

AF:

0.357

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.603

Gnomad4 EAS exome

AF:

0.363

Gnomad4 SAS exome

AF:

0.447

Gnomad4 FIN exome

AF:

0.584

Gnomad4 NFE exome

AF:

0.505

Gnomad4 OTH exome

AF:

0.490

GnomAD4 genome

AF:

0.447

AC:

67928

AN:

151838

Hom.:

15737

Cov.:

AF XY:

0.450

AC XY:

33408

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.591

Gnomad4 EAS

AF:

0.394

Gnomad4 SAS

AF:

0.427

Gnomad4 FIN

AF:

0.591

Gnomad4 NFE

AF:

0.501

Gnomad4 OTH

AF:

0.460

Alfa

AF:

0.468

Hom.:

4469

Bravo

AF:

0.426

Asia WGS

AF:

0.414

AC:

1440

AN:

3476

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

-0.90

CADD

Benign

0.81

DANN

Benign

0.49

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