chr20-34406909-A-G

Position:

• chr20-34406909-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374864.10(ITCH):​c.71-1742A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,932 control chromosomes in the GnomAD database, including 23,781 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23781 hom., cov: 31)
• Consequence: ITCH ENST00000374864.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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]

ENSG00000289720 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITCH	NM_031483.7	c.71-1742A>G		intron_variant		ENST00000374864.10	NP_113671.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITCH	ENST00000374864.10	c.71-1742A>G		intron_variant		1	NM_031483.7	ENSP00000363998.4
ENSG00000289720	ENST00000696979.1	n.71-1742A>G		intron_variant				ENSP00000513014.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83908 AN: 151814 Hom.: 23751 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.553 AC: 83993 AN: 151932 Hom.: 23781 Cov.: 31 AF XY: 0.550 AC XY: 40815 AN XY: 74246

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.542

Alfa AF: 0.502 Hom.: 4527

Bravo AF: 0.574

Asia WGS AF: 0.589 AC: 2048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.0
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs6579165; hg19: chr20-32994715;