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GeneBe

16-50749785-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001378743.1(CYLD):c.87C>T(p.Ser29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,613,752 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 33 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 33 hom. )

Consequence

CYLD
NM_001378743.1 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0280
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-50749785-C-T is Benign according to our data. Variant chr16-50749785-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 695378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-50749785-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.028 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1681/152138) while in subpopulation AFR AF= 0.0385 (1595/41472). AF 95% confidence interval is 0.0369. There are 33 homozygotes in gnomad4. There are 760 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1675 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYLDNM_001378743.1 linkuse as main transcriptc.87C>T p.Ser29= synonymous_variant 3/19 ENST00000427738.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYLDENST00000427738.8 linkuse as main transcriptc.87C>T p.Ser29= synonymous_variant 3/195 NM_001378743.1 A1Q9NQC7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1675
AN:
152020
Hom.:
33
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0384
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00386
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00268
AC:
668
AN:
249170
Hom.:
17
AF XY:
0.00207
AC XY:
280
AN XY:
135190
show subpopulations
Gnomad AFR exome
AF:
0.0377
Gnomad AMR exome
AF:
0.00209
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000354
Gnomad OTH exome
AF:
0.00116
GnomAD4 exome
AF:
0.00112
AC:
1632
AN:
1461614
Hom.:
33
Cov.:
32
AF XY:
0.000974
AC XY:
708
AN XY:
727106
show subpopulations
Gnomad4 AFR exome
AF:
0.0388
Gnomad4 AMR exome
AF:
0.00235
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000639
Gnomad4 OTH exome
AF:
0.00242
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1681
AN:
152138
Hom.:
33
Cov.:
32
AF XY:
0.0102
AC XY:
760
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0385
Gnomad4 AMR
AF:
0.00386
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00511
Hom.:
4
Bravo
AF:
0.0126
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000237

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 18, 2021- -
Benign, criteria provided, single submitterclinical testingInvitaeDec 24, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
9.0
Dann
Benign
0.71

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34564491; hg19: chr16-50783696; API