chr16-50741834-T-G

Variant names:

• chr16-50741834-T-G
• rs751919
• ENST00000563315.2:n.146-430A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000567728.3(CYLD-AS1):​n.176-430A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,036 control chromosomes in the GnomAD database, including 9,958 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 0.35 (9958 hom., cov: 33)
• Consequence: CYLD-AS1 ENST00000567728.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 7 publications found

Genes affected

CYLD-AS1 (HGNC:55352): (CYLD antisense RNA 1)

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]

CYLD Gene-Disease associations (from GenCC):

• Brooke-Spiegler syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial cylindromatosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Genomics England PanelApp
• frontotemporal dementia and/or amyotrophic lateral sclerosis 8

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• trichoepithelioma, multiple familial, 1

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• familial multiple trichoepithelioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000567728.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYLD-AS1	NR_184273.1		n.77+837A>C		intron	N/A
	CYLD-AS1	NR_184274.1		n.78-430A>C		intron	N/A
	CYLD-AS1	NR_184275.1		n.78-430A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYLD-AS1	ENST00000563315.2	TSL:5	n.146-430A>C		intron	N/A
	CYLD-AS1	ENST00000567728.3	TSL:3	n.176-430A>C		intron	N/A
	CYLD-AS1	ENST00000688175.2		n.203-430A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52859 AN: 151916 Hom.: 9960 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.348 AC: 52887 AN: 152036 Hom.: 9958 Cov.: 33 AF XY: 0.345 AC XY: 25621 AN XY: 74314

African (AFR) AF: 0.227 AC: 9405 AN: 41516

American (AMR) AF: 0.376 AC: 5741 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3468

East Asian (EAS) AF: 0.136 AC: 697 AN: 5136

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4824

European-Finnish (FIN) AF: 0.396 AC: 4188 AN: 10578

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28610 AN: 67912

Other (OTH) AF: 0.353 AC: 747 AN: 2114

Alfa AF: 0.252 Hom.: 656

Bravo AF: 0.339

Asia WGS AF: 0.198 AC: 685 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.0
DANN	Benign	0.72
PhyloP100		-0.60
PromoterAI		-0.11	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751919; hg19: chr16-50775745;