1-32203995-G-C

Variant names:

• chr1-32203995-G-C
• rs200163249
• NM_024296.5:c.281G>C

Variant summary

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

The NM_024296.5(CCDC28B):​c.281G>C​(p.Gly94Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,374 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G94E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CCDC28B NM_024296.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.75
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.281G>C	p.Gly94Ala	missense	Exon 3 of 6	NP_077272.2	Q9BUN5-1
	CCDC28B	NM_001301011.2		c.281G>C	p.Gly94Ala	missense	Exon 3 of 5	NP_001287940.1	Q9BUN5-3
	CCDC28B	NM_001437632.1		c.281G>C	p.Gly94Ala	missense	Exon 3 of 5	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.281G>C	p.Gly94Ala	missense	Exon 3 of 6	ENSP00000362704.5	Q9BUN5-1
	CCDC28B	ENST00000421922.6	TSL:1	c.281G>C	p.Gly94Ala	missense	Exon 3 of 5	ENSP00000413017.2	Q9BUN5-3
	CCDC28B	ENST00000868525.1		c.281G>C	p.Gly94Ala	missense	Exon 2 of 5	ENSP00000538584.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422374 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 704284

African (AFR) AF: 0.00 AC: 0 AN: 32142

American (AMR) AF: 0.00 AC: 0 AN: 38750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23372

East Asian (EAS) AF: 0.00 AC: 0 AN: 39280

South Asian (SAS) AF: 0.00 AC: 0 AN: 79572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52044

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5564

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092894

Other (OTH) AF: 0.00 AC: 0 AN: 58756

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0065	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.43
Sift	Benign	0.29	T
Sift4G	Benign	0.14	T
Polyphen		0.59	P
Vest4		0.86
MutPred		0.45		Loss of catalytic residue at E92 (P = 0.3082)
MVP		0.41
MPC		0.49
ClinPred		0.61	D
GERP RS		4.6
Varity_R		0.37
gMVP		0.58
Mutation Taster		=52/48	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: rs200163249; hg19: chr1-32669596;