chr20-34456979-C-T

Variant names:

• chr20-34456979-C-T
• rs6059850
• NM_031483.7:c.1211-411C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031483.7(ITCH):​c.1211-411C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: ITCH NM_031483.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• syndromic multisystem autoimmune disease due to ITCH deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000289720 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031483.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITCH	NM_031483.7	MANE Select	c.1211-411C>T		intron	N/A	NP_113671.3
	ITCH	NM_001257137.3		c.1334-411C>T		intron	N/A	NP_001244066.1
	ITCH	NM_001324197.2		c.1334-411C>T		intron	N/A	NP_001311126.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITCH	ENST00000374864.10	TSL:1 MANE Select	c.1211-411C>T		intron	N/A	ENSP00000363998.4
	ITCH	ENST00000262650.11	TSL:1	c.1334-411C>T		intron	N/A	ENSP00000262650.5
	ENSG00000289720	ENST00000696979.1		n.1211-411C>T		intron	N/A	ENSP00000513014.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150964 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150964 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73664

African (AFR) AF: 0.00 AC: 0 AN: 41152

American (AMR) AF: 0.00 AC: 0 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67812

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 2216

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.30

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

Other links and lift over

dbSNP: rs6059850; hg19: chr20-33044784;