rs11862720

Positions:

• chr16-50758793-C-G
• chr16-50758793-C-T

Variant summary

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

The NM_001378743.1(CYLD):​c.913+4369C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,804 control chromosomes in the GnomAD database, including 6,813 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 0.23 (6813 hom., cov: 32)
• Consequence: CYLD NM_001378743.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.71

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYLD	NM_001378743.1	c.913+4369C>G		intron_variant		ENST00000427738.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYLD	ENST00000427738.8	c.913+4369C>G		intron_variant		5	NM_001378743.1	A1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35219 AN: 151686 Hom.: 6779 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.233 AC: 35310 AN: 151804 Hom.: 6813 Cov.: 32 AF XY: 0.231 AC XY: 17141 AN XY: 74186

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0908

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.186

Alfa AF: 0.0523 Hom.: 61

Bravo AF: 0.245

Asia WGS AF: 0.190 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.056
DANN	Benign	0.41

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: rs11862720; hg19: chr16-50792704;