dbSNP rs6425793: CCDC28B:c.164+728A>G (chr1-32202827-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024296.5(CCDC28B):c.164+728A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 155,446 control chromosomes in the GnomAD database, including 4,410 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4286 hom., cov: 32)

Exomes 𝑓: 0.27 ( 124 hom. )

Consequence

CCDC28B
NM_024296.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.243

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024296.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC28B	NM_024296.5	MANE Select	c.164+728A>G	intron	N/A	NP_077272.2	Q9BUN5-1
CCDC28B	NM_001301011.2		c.164+728A>G	intron	N/A	NP_001287940.1	Q9BUN5-3
CCDC28B	NM_001437632.1		c.164+728A>G	intron	N/A	NP_001424561.1	A0A7P0TB33

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC28B	ENST00000373602.10	TSL:1 MANE Select	c.164+728A>G	intron	N/A	ENSP00000362704.5	Q9BUN5-1
CCDC28B	ENST00000421922.6	TSL:1	c.164+728A>G	intron	N/A	ENSP00000413017.2	Q9BUN5-3
CCDC28B	ENST00000868525.1		c.164+728A>G	intron	N/A	ENSP00000538584.1

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32529

AN:

152086

Hom.:

4285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.273

AC:

886

AN:

3242

Hom.:

124

Cov.:

AF XY:

0.268

AC XY:

470

AN XY:

1752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.283

AC:

147

AN:

520

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

AN:

East Asian (EAS)

AF:

0.130

AC:

AN:

South Asian (SAS)

AF:

0.211

AC:

AN:

294

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.284

AC:

629

AN:

2214

Other (OTH)

AF:

0.287

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.214

AC:

32536

AN:

152204

Hom.:

4286

Cov.:

AF XY:

0.211

AC XY:

15737

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0545

AC:

2265

AN:

41522

American (AMR)

AF:

0.255

AC:

3903

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

880

AN:

3472

East Asian (EAS)

AF:

0.166

AC:

862

AN:

5182

South Asian (SAS)

AF:

0.271

AC:

1309

AN:

4830

European-Finnish (FIN)

AF:

0.235

AC:

2493

AN:

10588

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19945

AN:

67996

Other (OTH)

AF:

0.228

AC:

482

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1277

2554

3831

5108

6385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.194

Hom.:

1475

Bravo

AF:

0.209

Asia WGS

AF:

0.212

AC:

737

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

(source)

DANN

Benign

0.67

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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