16-50781521-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378743.1(CYLD):c.1684+110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,343,566 control chromosomes in the GnomAD database, including 6,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (490 hom., cov: 32)
  • Exomes 𝑓: 0.089 (6049 hom.)
• Consequence: CYLD NM_001378743.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.432

Genes affected

CYLD (HGNC:2584): (CYLD lysine 63 deubiquitinase) This gene is encodes a cytoplasmic protein with three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains that functions as a deubiquitinating enzyme. Mutations in this gene have been associated with cylindromatosis, multiple familial trichoepithelioma, and Brooke-Spiegler syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-50781521-C-T is Benign according to our data. Variant chr16-50781521-C-T is described in ClinVar as [Benign]. Clinvar id is 1267104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYLD	NM_001378743.1	c.1684+110C>T		intron_variant		ENST00000427738.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYLD	ENST00000427738.8	c.1684+110C>T		intron_variant		5	NM_001378743.1	A1

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10290 AN: 152106 Hom.: 491 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.0833

GnomAD4 exome AF: 0.0885 AC: 105457 AN: 1191342 Hom.: 6049 AF XY: 0.0947 AC XY: 56779 AN XY: 599666

Gnomad4 AFR exome AF: 0.0310

Gnomad4 AMR exome AF: 0.0493

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.0643

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.0503

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.0930

GnomAD4 genome AF: 0.0676 AC: 10295 AN: 152224 Hom.: 490 Cov.: 32 AF XY: 0.0695 AC XY: 5176 AN XY: 74432

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.0607

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0483

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0801

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.0406 Hom.: 53

Bravo AF: 0.0630

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.5
Dann	Benign	0.60

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: rs1420871; hg19: chr16-50815432; COSMIC: COSV61097347; COSMIC: COSV61097347;