1-32204332-C-G

Variant names:

• chr1-32204332-C-G
• rs1553139012
• NM_024296.5:c.478C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024296.5(CCDC28B):​c.478C>G​(p.Gln160Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q160K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC28B NM_024296.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13411656).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC28B	NM_024296.5	MANE Select	c.478C>G	p.Gln160Glu	missense	Exon 4 of 6	NP_077272.2	Q9BUN5-1
	CCDC28B	NM_001301011.2		c.478C>G	p.Gln160Glu	missense	Exon 4 of 5	NP_001287940.1	Q9BUN5-3
	CCDC28B	NM_001437632.1		c.332-266C>G		intron	N/A	NP_001424561.1	A0A7P0TB33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC28B	ENST00000373602.10	TSL:1 MANE Select	c.478C>G	p.Gln160Glu	missense	Exon 4 of 6	ENSP00000362704.5	Q9BUN5-1
	CCDC28B	ENST00000421922.6	TSL:1	c.478C>G	p.Gln160Glu	missense	Exon 4 of 5	ENSP00000413017.2	Q9BUN5-3
	CCDC28B	ENST00000868525.1		c.478C>G	p.Gln160Glu	missense	Exon 3 of 5	ENSP00000538584.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454052 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 722834

African (AFR) AF: 0.00 AC: 0 AN: 33280

American (AMR) AF: 0.00 AC: 0 AN: 43810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25436

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107886

Other (OTH) AF: 0.00 AC: 0 AN: 60022

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T
Eigen	Benign	0.038
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.14
Sift	Benign	0.23	T
Sift4G	Benign	0.56	T
Polyphen		0.79	P
Vest4		0.42
MutPred		0.094		Loss of methylation at K161 (P = 0.0816)
MVP		0.26
MPC		0.62
ClinPred		0.50	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.13
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs1553139012; hg19: chr1-32669933; COSMIC: COSV52207614; COSMIC: COSV52207614;