rs1548990

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYLD	NM_001378743.1	c.-124+2587T>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.-124+2587T>C		intron_variant		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

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.536

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

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: rs1548990; hg19: chr16-50779339;