Variant chr1-32204317-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024296.5(CCDC28B):c.463G>A(p.Gly155Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,611,476 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 36 hom. )

Consequence

CCDC28B
NM_024296.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.65

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060026944).

BP6

Variant 1-32204317-G-A is Benign according to our data. Variant chr1-32204317-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 281760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-32204317-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 750 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC28B	NM_024296.5 linkuse as main transcript	c.463G>A	p.Gly155Arg	missense_variant	4/6	ENST00000373602.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC28B	ENST00000373602.10 linkuse as main transcript	c.463G>A	p.Gly155Arg	missense_variant	4/6	1	NM_024296.5	P1	Q9BUN5-1

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

750

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00961

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00785

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00553

AC:

1371

AN:

247914

Hom.:

AF XY:

0.00557

AC XY:

746

AN XY:

133950

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.000515

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000332

Gnomad FIN exome

AF:

0.0113

Gnomad NFE exome

AF:

0.00902

Gnomad OTH exome

AF:

0.00548

GnomAD4 exome

AF:

0.00636

AC:

9277

AN:

1459244

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

4521

AN XY:

725790

show subpopulations

Gnomad4 AFR exome

AF:

0.000719

Gnomad4 AMR exome

AF:

0.00216

Gnomad4 ASJ exome

AF:

0.000734

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000314

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.00741

Gnomad4 OTH exome

AF:

0.00410

GnomAD4 genome

AF:

0.00493

AC:

750

AN:

152232

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

358

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00961

Gnomad4 NFE

AF:

0.00785

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00683

Hom.:

Bravo

AF:

0.00447

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00604

AC:

733

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Oct 22, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	CCDC28B: BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 14, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.11

Sift

Benign

0.071

T;D

Sift4G

Benign

0.091

T;D

Polyphen

0.98

D;.

Vest4

0.25

MutPred

0.10

Gain of phosphorylation at T153 (P = 0.107);Gain of phosphorylation at T153 (P = 0.107);

MVP

0.30

MPC

0.70

ClinPred

0.0096

GERP RS

4.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.15

gMVP

0.048

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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