16-50747891-T-C

Position:

• chr16-50747891-T-C

Variant summary

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

The NM_001378743.1(CYLD):​c.-123-1685T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,122 control chromosomes in the GnomAD database, including 10,555 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 0.36 (10555 hom., cov: 32)
• Consequence: CYLD NM_001378743.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYLD	NM_001378743.1	c.-123-1685T>C		intron_variant		ENST00000427738.8	NP_001365672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYLD	ENST00000427738.8	c.-123-1685T>C		intron_variant		5	NM_001378743.1	ENSP00000392025	A1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54444 AN: 152004 Hom.: 10555 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.358 AC: 54467 AN: 152122 Hom.: 10555 Cov.: 32 AF XY: 0.356 AC XY: 26498 AN XY: 74354

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.368

Alfa AF: 0.401 Hom.: 7009

Bravo AF: 0.355

Asia WGS AF: 0.206 AC: 715 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	1.5
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: rs8060598; hg19: chr16-50781802;