Variant chr1-32202008-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024296.5(CCDC28B):c.73C>T(p.Arg25Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0251 in 1,613,614 control chromosomes in the GnomAD database, including 754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.036 ( 141 hom., cov: 32)

Exomes 𝑓: 0.024 ( 613 hom. )

Consequence

CCDC28B
NM_024296.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

CCDC28B (HGNC:28163): (coiled-coil domain containing 28B) The product of this gene localizes to centrosomes and basal bodies. The protein colocalizes with several proteins associated with Bardet-Biedl syndrome (BBS) and participates in the regulation of cilia development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CCDC28B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036373138).

BP6

Variant 1-32202008-C-T is Benign according to our data. Variant chr1-32202008-C-T is described in ClinVar as [Benign]. Clinvar id is 1271446.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-32202008-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC28B	NM_024296.5 linkuse as main transcript	c.73C>T	p.Arg25Trp	missense_variant	2/6	ENST00000373602.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC28B	ENST00000373602.10 linkuse as main transcript	c.73C>T	p.Arg25Trp	missense_variant	2/6	1	NM_024296.5	P1	Q9BUN5-1

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5533

AN:

152152

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.0640

Gnomad EAS

AF:

0.0391

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0511

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0349

GnomAD3 exomes

AF:

0.0326

AC:

8168

AN:

250196

Hom.:

190

AF XY:

0.0338

AC XY:

4574

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.0523

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0644

Gnomad EAS exome

AF:

0.0393

Gnomad SAS exome

AF:

0.0480

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0243

Gnomad OTH exome

AF:

0.0306

GnomAD4 exome

AF:

0.0239

AC:

34912

AN:

1461344

Hom.:

613

Cov.:

AF XY:

0.0247

AC XY:

17976

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.0133

Gnomad4 ASJ exome

AF:

0.0656

Gnomad4 EAS exome

AF:

0.0268

Gnomad4 SAS exome

AF:

0.0493

Gnomad4 FIN exome

AF:

0.0476

Gnomad4 NFE exome

AF:

0.0186

Gnomad4 OTH exome

AF:

0.0301

GnomAD4 genome

AF:

0.0363

AC:

5535

AN:

152270

Hom.:

141

Cov.:

AF XY:

0.0379

AC XY:

2823

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0547

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0640

Gnomad4 EAS

AF:

0.0386

Gnomad4 SAS

AF:

0.0487

Gnomad4 FIN

AF:

0.0511

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0261

Hom.:

149

Bravo

AF:

0.0344

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0176

AC:

ESP6500AA

AF:

0.0531

AC:

234

ESP6500EA

AF:

0.0251

AC:

216

ExAC

AF:

0.0332

AC:

4026

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

EpiCase

AF:

0.0248

EpiControl

AF:

0.0286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;.

Vest4

0.47

MPC

1.0

ClinPred

0.029

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over