16-50787056-G-A

Variant names:

• chr16-50787056-G-A
• rs12599914
• NM_001378743.1:c.2041+110G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378743.1(CYLD):​c.2041+110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 925,184 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (341 hom., cov: 33)
  • Exomes 𝑓: 0.0083 (248 hom.)
• Consequence: CYLD NM_001378743.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.196
• Publications: 0 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-AS2 (HGNC:56848): (CYLD antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-50787056-G-A is Benign according to our data. Variant chr16-50787056-G-A is described in ClinVar as Benign. ClinVar VariationId is 1275227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378743.1. 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	NM_001378743.1	MANE Select	c.2041+110G>A		intron	N/A	NP_001365672.1	Q9NQC7-1
	CYLD	NM_015247.3		c.2041+110G>A		intron	N/A	NP_056062.1	Q9NQC7-1
	CYLD	NM_001042355.2		c.2032+110G>A		intron	N/A	NP_001035814.1	Q9NQC7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYLD	ENST00000427738.8	TSL:5 MANE Select	c.2041+110G>A		intron	N/A	ENSP00000392025.3	Q9NQC7-1
	CYLD	ENST00000398568.6	TSL:1	c.2032+110G>A		intron	N/A	ENSP00000381574.2	Q9NQC7-2
	CYLD	ENST00000569418.5	TSL:1	c.2032+110G>A		intron	N/A	ENSP00000457576.1	Q9NQC7-2

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5880 AN: 152094 Hom.: 340 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0144 AC: 2766 AN: 192030 AF XY: 0.0116

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.00921

Gnomad ASJ exome AF: 0.00138

Gnomad EAS exome AF: 0.0528

Gnomad FIN exome AF: 0.0000556

Gnomad NFE exome AF: 0.00232

Gnomad OTH exome AF: 0.00896

GnomAD4 exome AF: 0.00830 AC: 6415 AN: 772972 Hom.: 248 Cov.: 10 AF XY: 0.00743 AC XY: 3034 AN XY: 408448

African (AFR) AF: 0.130 AC: 2493 AN: 19238

American (AMR) AF: 0.00941 AC: 350 AN: 37214

Ashkenazi Jewish (ASJ) AF: 0.00194 AC: 41 AN: 21134

East Asian (EAS) AF: 0.0505 AC: 1794 AN: 35514

South Asian (SAS) AF: 0.00179 AC: 123 AN: 68760

European-Finnish (FIN) AF: 0.000121 AC: 6 AN: 49472

Middle Eastern (MID) AF: 0.0180 AC: 64 AN: 3558

European-Non Finnish (NFE) AF: 0.00223 AC: 1117 AN: 500852

Other (OTH) AF: 0.0115 AC: 427 AN: 37230

GnomAD4 genome AF: 0.0387 AC: 5890 AN: 152212 Hom.: 341 Cov.: 33 AF XY: 0.0388 AC XY: 2888 AN XY: 74436

African (AFR) AF: 0.125 AC: 5206 AN: 41500

American (AMR) AF: 0.0126 AC: 193 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5184

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 68012

Other (OTH) AF: 0.0289 AC: 61 AN: 2108

Alfa AF: 0.0228 Hom.: 40

Bravo AF: 0.0437

Asia WGS AF: 0.0210 AC: 74 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		-0.20
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: rs12599914; hg19: chr16-50820967;