dbSNP rs1362698: CYLD:c.-124+550C>T (chr16-50743391-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001378743.1(CYLD):c.-124+550C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,150 control chromosomes in the GnomAD database, including 2,640 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 0.10 ( 2640 hom., cov: 32)

Consequence

CYLD
NM_001378743.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.335

Publications

1 publications found

Variant links:

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

CYLD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYLD	NM_001378743.1 link	c.-124+550C>T		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 link	c.-124+550C>T		intron_variant	Intron 2 of 18	5	NM_001378743.1	ENSP00000392025.3		Q9NQC7-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15609

AN:

152032

Hom.:

2618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0383

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00269

Gnomad OTH

AF:

0.0579

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

GnomAD4 genome

AF:

0.103

AC:

15678

AN:

152150

Hom.:

2640

Cov.:

AF XY:

0.0986

AC XY:

7332

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.356

AC:

14760

AN:

41432

American (AMR)

AF:

0.0382

AC:

584

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00228

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00269

AC:

183

AN:

68016

Other (OTH)

AF:

0.0573

AC:

121

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

531

1061

1592

2122

2653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0433

Hom.:

2707

Bravo

AF:

0.119

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over