chr1-32201994-C-T

Variant names:

• chr1-32201994-C-T
• NM_024296.5:c.59C>T

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.59C>T​(p.Ala20Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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)
• Consequence: CCDC28B NM_024296.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17
• 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=0.070506245).

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.59C>T	p.Ala20Val	missense	Exon 2 of 6	NP_077272.2	Q9BUN5-1
	CCDC28B	NM_001301011.2		c.59C>T	p.Ala20Val	missense	Exon 2 of 5	NP_001287940.1	Q9BUN5-3
	CCDC28B	NM_001437632.1		c.59C>T	p.Ala20Val	missense	Exon 2 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.59C>T	p.Ala20Val	missense	Exon 2 of 6	ENSP00000362704.5	Q9BUN5-1
	CCDC28B	ENST00000421922.6	TSL:1	c.59C>T	p.Ala20Val	missense	Exon 2 of 5	ENSP00000413017.2	Q9BUN5-3
	CCDC28B	ENST00000868525.1		c.59C>T	p.Ala20Val	missense	Exon 1 of 5	ENSP00000538584.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.0028
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.10
Sift	Benign	0.90	T
Sift4G	Benign	0.53	T
Polyphen		0.18	B
Vest4		0.15
MutPred		0.078		Gain of catalytic residue at A20 (P = 0.0796)
MVP		0.28
MPC		0.39
ClinPred		0.90	D
GERP RS		4.5
Varity_R		0.19
gMVP		0.31
Mutation Taster		=90/10	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

hg19: chr1-32667595;