rs3736762

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

2

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]

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
ITCHNM_031483.7 linkuse as main transcriptc.1210+51C>T intron_variant ENST00000374864.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITCHENST00000374864.10 linkuse as main transcriptc.1210+51C>T intron_variant 1 NM_031483.7 P1Q96J02-2

Frequencies

GnomAD3 genomes
AF:
0.447
AC:
67888
AN:
151720
Hom.:
15730
Cov.:
31
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.:
14
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.:
31
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 submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanNov 12, 2023This 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.

Other links and lift over

dbSNP: rs3736762; hg19: chr20-33037336; COSMIC: COSV52932237; COSMIC: COSV52932237; API