rs1548990

Variant names:

• chr16-50745428-T-C
• rs1548990
• NM_001378743.1:c.-124+2587T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-50745428-T-C
• chr16-50745428-T-G

Variant summary

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

The NM_001378743.1(CYLD):​c.-124+2587T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 145,912 control chromosomes in the GnomAD database, including 24,656 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 0.57 (24656 hom., cov: 21)
• Consequence: CYLD NM_001378743.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 1 publications found

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]

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYLD	NM_001378743.1	c.-124+2587T>C		intron_variant	Intron 2 of 18	ENST00000427738.8	NP_001365672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYLD	ENST00000427738.8	c.-124+2587T>C		intron_variant	Intron 2 of 18	5	NM_001378743.1	ENSP00000392025.3

Frequencies

GnomAD3 genomes AF: 0.568 AC: 82775 AN: 145802 Hom.: 24599 Cov.: 21

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.546

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.568 AC: 82887 AN: 145912 Hom.: 24656 Cov.: 21 AF XY: 0.564 AC XY: 39856 AN XY: 70608

African (AFR) AF: 0.748 AC: 29043 AN: 38840

American (AMR) AF: 0.495 AC: 7157 AN: 14466

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2275 AN: 3444

East Asian (EAS) AF: 0.228 AC: 1135 AN: 4980

South Asian (SAS) AF: 0.469 AC: 2112 AN: 4508

European-Finnish (FIN) AF: 0.515 AC: 4861 AN: 9446

Middle Eastern (MID) AF: 0.535 AC: 152 AN: 284

European-Non Finnish (NFE) AF: 0.515 AC: 34551 AN: 67044

Other (OTH) AF: 0.536 AC: 1080 AN: 2014

Alfa AF: 0.520 Hom.: 2565

Bravo AF: 0.573

Asia WGS AF: 0.391 AC: 1362 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	0.90
DANN	Benign	0.47
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1548990; hg19: chr16-50779339;