Variant chr1-32204354-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024296.5(CCDC28B):c.500G>A(p.Arg167His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,440,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000012 ( 0 hom. )

Consequence

CCDC28B
NM_024296.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13438773).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC28B	NM_024296.5 linkuse as main transcript	c.500G>A	p.Arg167His	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.500G>A	p.Arg167His	missense_variant	4/6	1	NM_024296.5	P1	Q9BUN5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000867

AC:

AN:

230674

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123774

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1440338

Hom.:

Cov.:

AF XY:

0.00000979

AC XY:

AN XY:

714756

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2022

The c.500G>A (p.R167H) alteration is located in exon 4 (coding exon 3) of the CCDC28B gene. This alteration results from a G to A substitution at nucleotide position 500, causing the arginine (R) at amino acid position 167 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.077

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.94

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;D

Sift4G

Benign

0.14

T;T

Polyphen

0.0030

B;.

Vest4

0.12

MutPred

0.093

Gain of catalytic residue at N168 (P = 0.0806);Gain of catalytic residue at N168 (P = 0.0806);

MVP

0.21

MPC

0.39

ClinPred

0.12

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.029

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