Genetic Variant CCDC28B:p.Gln160Lys (chr1-32204332-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024296.5(CCDC28B):c.478C>A(p.Gln160Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,454,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CCDC28B
NM_024296.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06439474).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC28B	NM_024296.5	MANE Select	c.478C>A	p.Gln160Lys	missense	Exon 4 of 6	NP_077272.2	Q9BUN5-1
CCDC28B	NM_001301011.2		c.478C>A	p.Gln160Lys	missense	Exon 4 of 5	NP_001287940.1	Q9BUN5-3
CCDC28B	NM_001437632.1		c.332-266C>A		intron	N/A	NP_001424561.1	A0A7P0TB33

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC28B	ENST00000373602.10	TSL:1 MANE Select	c.478C>A	p.Gln160Lys	missense	Exon 4 of 6	ENSP00000362704.5	Q9BUN5-1
CCDC28B	ENST00000421922.6	TSL:1	c.478C>A	p.Gln160Lys	missense	Exon 4 of 5	ENSP00000413017.2	Q9BUN5-3
CCDC28B	ENST00000868525.1		c.478C>A	p.Gln160Lys	missense	Exon 3 of 5	ENSP00000538584.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

242332

AF XY:

0.0000153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1454050

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

722832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33280

American (AMR)

AF:

0.00

AC:

AN:

43810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25436

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

85132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

1107884

Other (OTH)

AF:

0.00

AC:

AN:

60022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.031

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.63

M_CAP

Benign

0.0086

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

2.8

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.090

REVEL

Benign

0.049

Sift

Benign

0.63

Sift4G

Benign

0.87

Polyphen

0.13

Vest4

0.25

MutPred

0.17

Gain of ubiquitination at Q160 (P = 0.0104)

MVP

0.19

MPC

0.70

ClinPred

0.17

GERP RS

3.9

Varity_R

0.30

gMVP

0.22

Mutation Taster

=87/13

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over