Genetic Variant NM_024296.5:c.330C>T (chr1-32204044-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_024296.5(CCDC28B):c.330C>T(p.Phe110Phe) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,554,330 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.010 ( 25 hom., cov: 32)

Exomes 𝑓: 0.013 ( 211 hom. )

Consequence

CCDC28B
NM_024296.5 splice_region, synonymous

Scores

Splicing: ADA: 0.004443

Clinical Significance

Uncertain significance criteria provided, single submitter U:2O:1

Conservation

PhyloP100: -1.46

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 1
Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

CCDC28B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC28B	NM_024296.5 link	c.330C>T	p.Phe110Phe	splice_region_variant, synonymous_variant	Exon 3 of 6	ENST00000373602.10	NP_077272.2	Q9BUN5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC28B	ENST00000373602.10 link	c.330C>T	p.Phe110Phe	splice_region_variant, synonymous_variant	Exon 3 of 6	1	NM_024296.5	ENSP00000362704.5		Q9BUN5-1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1591

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00290

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0645

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0116

AC:

2358

AN:

203610

AF XY:

0.0122

show subpopulations

Gnomad AFR exome

AF:

0.00218

Gnomad AMR exome

AF:

0.00883

Gnomad ASJ exome

AF:

0.0689

Gnomad EAS exome

AF:

0.0000587

Gnomad FIN exome

AF:

0.000908

Gnomad NFE exome

AF:

0.0145

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0131

AC:

18358

AN:

1402106

Hom.:

211

Cov.:

AF XY:

0.0132

AC XY:

9120

AN XY:

691058

show subpopulations

African (AFR)

AF:

0.00449

AC:

142

AN:

31658

American (AMR)

AF:

0.00931

AC:

341

AN:

36640

Ashkenazi Jewish (ASJ)

AF:

0.0676

AC:

1493

AN:

22072

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39020

South Asian (SAS)

AF:

0.0108

AC:

829

AN:

76468

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

51304

Middle Eastern (MID)

AF:

0.0638

AC:

349

AN:

5466

European-Non Finnish (NFE)

AF:

0.0131

AC:

14149

AN:

1081662

Other (OTH)

AF:

0.0172

AC:

996

AN:

57816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

949

1898

2848

3797

4746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.0105

AC:

1591

AN:

152224

Hom.:

Cov.:

AF XY:

0.00978

AC XY:

728

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00289

AC:

120

AN:

41532

American (AMR)

AF:

0.0143

AC:

219

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0645

AC:

224

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00705

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0136

AC:

923

AN:

68016

Other (OTH)

AF:

0.0175

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0144

Hom.:

100

Bravo

AF:

0.0112

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCDC28B-related disorder

Uncertain:1

Apr 19, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Bardet-Biedl syndrome

Uncertain:1

Tolun Lab, Human Genetics Laboratory, Bogazici University

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Bardet-Biedl syndrome 1, modifier of

Other:1

Jan 19, 2006

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.6

(source)

DANN

Benign

0.76

PhyloP100

-1.5

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0044

dbscSNV1_RF

Benign

0.65

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over