rs6088512

Positions:

• chr20-34508086-G-A

Variant summary

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

The ENST00000374864.10(ITCH):​c.*292G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 374,436 control chromosomes in the GnomAD database, including 45,949 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 0.48 (17901 hom., cov: 32)
  • Exomes 𝑓: 0.50 (28048 hom.)
• Consequence: ITCH ENST00000374864.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITCH	NM_031483.7	c.*292G>A		3_prime_UTR_variant	25/25	ENST00000374864.10	NP_113671.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITCH	ENST00000374864.10	c.*292G>A		3_prime_UTR_variant	25/25	1	NM_031483.7	ENSP00000363998	P1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73120 AN: 151978 Hom.: 17879 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.498 AC: 110617 AN: 222340 Hom.: 28048 Cov.: 0 AF XY: 0.497 AC XY: 59855 AN XY: 120472

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.599

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.481 AC: 73182 AN: 152096 Hom.: 17901 Cov.: 32 AF XY: 0.484 AC XY: 35994 AN XY: 74338

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.490

Alfa AF: 0.500 Hom.: 18672

Bravo AF: 0.463

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.43

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: rs6088512; hg19: chr20-33095891;