chr16-50749517-A-G

Position:

• chr16-50749517-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378743.1(CYLD):​c.-123-59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 622,130 control chromosomes in the GnomAD database, including 911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (675 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (236 hom.)
• Consequence: CYLD NM_001378743.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.59

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 16-50749517-A-G is Benign according to our data. Variant chr16-50749517-A-G is described in ClinVar as [Benign]. Clinvar id is 1280234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYLD	NM_001378743.1	c.-123-59A>G		intron_variant		ENST00000427738.8	NP_001365672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYLD	ENST00000427738.8	c.-123-59A>G		intron_variant		5	NM_001378743.1	ENSP00000392025	A1

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7963 AN: 152166 Hom.: 671 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.00786 AC: 3695 AN: 469846 Hom.: 236 Cov.: 5 AF XY: 0.00680 AC XY: 1682 AN XY: 247342

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.00366

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000767

Gnomad4 FIN exome AF: 0.0000675

Gnomad4 NFE exome AF: 0.00205

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0525 AC: 7994 AN: 152284 Hom.: 675 Cov.: 32 AF XY: 0.0499 AC XY: 3717 AN XY: 74464

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0121 Hom.: 37

Bravo AF: 0.0614

Asia WGS AF: 0.0120 AC: 41 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.92

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: rs7187352; hg19: chr16-50783428;