rs3740370

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018131.5(CEP55):c.171C>G(p.His57Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,607,764 control chromosomes in the GnomAD database, including 41,389 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4363 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37026 hom. )

Consequence

CEP55
NM_018131.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.448

Publications

31 publications found

Variant links:

Genes affected

CEP55 (HGNC:1161): (centrosomal protein 55) Enables identical protein binding activity. Involved in cranial skeletal system development; establishment of protein localization; and midbody abscission. Acts upstream of or within mitotic cytokinesis. Located in Flemming body; centriolar satellite; and plasma membrane. Implicated in multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly. [provided by Alliance of Genome Resources, Apr 2022]

CEP55 Gene-Disease associations (from GenCC):

multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

CEP55 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0036286712).

BP6

Variant 10-93500222-C-G is Benign according to our data. Variant chr10-93500222-C-G is described in ClinVar as Benign. ClinVar VariationId is 1593062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018131.5. 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
	CEP55	NM_018131.5	MANE Select	c.171C>G	p.His57Gln	missense	Exon 2 of 9	NP_060601.4
	CEP55	NM_001127182.2		c.171C>G	p.His57Gln	missense	Exon 2 of 9	NP_001120654.2	Q53EZ4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP55	ENST00000371485.8	TSL:1 MANE Select	c.171C>G	p.His57Gln	missense	Exon 2 of 9	ENSP00000360540.3	Q53EZ4-1
CEP55	ENST00000897343.1		c.171C>G	p.His57Gln	missense	Exon 2 of 9	ENSP00000567402.1
CEP55	ENST00000912346.1		c.171C>G	p.His57Gln	missense	Exon 2 of 9	ENSP00000582405.1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35899

AN:

151932

Hom.:

4357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.242

GnomAD2 exomes

AF:

0.218

AC:

54051

AN:

247410

AF XY:

0.225

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.222

AC:

322894

AN:

1455714

Hom.:

37026

Cov.:

AF XY:

0.225

AC XY:

162889

AN XY:

724400

show subpopulations

African (AFR)

AF:

0.286

AC:

9433

AN:

33002

American (AMR)

AF:

0.123

AC:

5363

AN:

43432

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

7885

AN:

25990

East Asian (EAS)

AF:

0.279

AC:

11071

AN:

39618

South Asian (SAS)

AF:

0.270

AC:

23036

AN:

85394

European-Finnish (FIN)

AF:

0.183

AC:

9736

AN:

53324

Middle Eastern (MID)

AF:

0.285

AC:

1638

AN:

5744

European-Non Finnish (NFE)

AF:

0.217

AC:

240777

AN:

1109072

Other (OTH)

AF:

0.232

AC:

13955

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

11637

23275

34912

46550

58187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8416

16832

25248

33664

42080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.236

AC:

35924

AN:

152050

Hom.:

4363

Cov.:

AF XY:

0.236

AC XY:

17518

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.283

AC:

11748

AN:

41460

American (AMR)

AF:

0.172

AC:

2625

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1066

AN:

3464

East Asian (EAS)

AF:

0.277

AC:

1432

AN:

5164

South Asian (SAS)

AF:

0.273

AC:

1316

AN:

4818

European-Finnish (FIN)

AF:

0.179

AC:

1893

AN:

10566

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.222

AC:

15068

AN:

67980

Other (OTH)

AF:

0.242

AC:

510

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1389

2778

4168

5557

6946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.233

Hom.:

3234

Bravo

AF:

0.236

TwinsUK

AF:

0.219

AC:

812

ALSPAC

AF:

0.214

AC:

823

ESP6500AA

AF:

0.287

AC:

1263

ESP6500EA

AF:

0.227

AC:

1955

ExAC

AF:

0.225

AC:

27283

Asia WGS

AF:

0.261

AC:

905

AN:

3478

EpiCase

AF:

0.234

EpiControl

AF:

0.232

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CEP55-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0036

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

PhyloP100

-0.45

PrimateAI

Benign

0.31

PROVEAN

Benign

0.24

REVEL

Benign

0.054

Sift

Benign

0.66

Sift4G

Benign

0.56

Polyphen

0.0010

Vest4

0.040

MutPred

0.31

Gain of MoRF binding (P = 0.0905)

MPC

0.15

ClinPred

0.00030

GERP RS

-1.1

Varity_R

0.034

gMVP

0.049

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over