rs1420873

Positions:

• chr16-50769845-G-C

Variant summary

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

The NM_001378743.1(CYLD):​c.914-5321G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,028 control chromosomes in the GnomAD database, including 6,604 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 (6604 hom., cov: 32)
• Consequence: CYLD NM_001378743.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYLD	NM_001378743.1	c.914-5321G>C		intron_variant		ENST00000427738.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYLD	ENST00000427738.8	c.914-5321G>C		intron_variant		5	NM_001378743.1	A1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34848 AN: 151910 Hom.: 6570 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.230 AC: 34940 AN: 152028 Hom.: 6604 Cov.: 32 AF XY: 0.228 AC XY: 16954 AN XY: 74310

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0893

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.184

Alfa AF: 0.176 Hom.: 518

Bravo AF: 0.242

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.24

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: rs1420873; hg19: chr16-50803756;