rs41263993

Variant names:

• chr1-32204044-C-T
• rs41263993
• NM_024296.5:c.330C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024296.5(CCDC28B):​c.330C>T​(p.Phe110Phe) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,554,330 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.010 (25 hom., cov: 32)
  • Exomes 𝑓: 0.013 (211 hom.)
• Consequence: CCDC28B NM_024296.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.004443
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2 O:1
• Conservation: PhyloP100: -1.46
• Publications: 11 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

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.330C>T	p.Phe110Phe	splice_region synonymous	Exon 3 of 6	NP_077272.2	Q9BUN5-1
	CCDC28B	NM_001301011.2		c.330C>T	p.Phe110Phe	splice_region synonymous	Exon 3 of 5	NP_001287940.1	Q9BUN5-3
	CCDC28B	NM_001437632.1		c.330C>T	p.Phe110Phe	splice_region synonymous	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.330C>T	p.Phe110Phe	splice_region synonymous	Exon 3 of 6	ENSP00000362704.5	Q9BUN5-1
	CCDC28B	ENST00000421922.6	TSL:1	c.330C>T	p.Phe110Phe	splice_region synonymous	Exon 3 of 5	ENSP00000413017.2	Q9BUN5-3
	CCDC28B	ENST00000868525.1		c.330C>T	p.Phe110Phe	splice_region synonymous	Exon 2 of 5	ENSP00000538584.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1591 AN: 152106 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0645

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.0116 AC: 2358 AN: 203610 AF XY: 0.0122

Gnomad AFR exome AF: 0.00218

Gnomad AMR exome AF: 0.00883

Gnomad ASJ exome AF: 0.0689

Gnomad EAS exome AF: 0.0000587

Gnomad FIN exome AF: 0.000908

Gnomad NFE exome AF: 0.0145

Gnomad OTH exome AF: 0.0202

GnomAD4 exome AF: 0.0131 AC: 18358 AN: 1402106 Hom.: 211 Cov.: 32 AF XY: 0.0132 AC XY: 9120 AN XY: 691058

African (AFR) AF: 0.00449 AC: 142 AN: 31658

American (AMR) AF: 0.00931 AC: 341 AN: 36640

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 1493 AN: 22072

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39020

South Asian (SAS) AF: 0.0108 AC: 829 AN: 76468

European-Finnish (FIN) AF: 0.00113 AC: 58 AN: 51304

Middle Eastern (MID) AF: 0.0638 AC: 349 AN: 5466

European-Non Finnish (NFE) AF: 0.0131 AC: 14149 AN: 1081662

Other (OTH) AF: 0.0172 AC: 996 AN: 57816

GnomAD4 genome AF: 0.0105 AC: 1591 AN: 152224 Hom.: 25 Cov.: 32 AF XY: 0.00978 AC XY: 728 AN XY: 74430

African (AFR) AF: 0.00289 AC: 120 AN: 41532

American (AMR) AF: 0.0143 AC: 219 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 224 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4820

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0136 AC: 923 AN: 68016

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0144 Hom.: 100

Bravo AF: 0.0112

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Bardet-Biedl syndrome (1)
-	1	-	CCDC28B-related disorder (1)
-	-	-	Bardet-Biedl syndrome 1, modifier of (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.6
DANN	Benign	0.76
PhyloP100		-1.5
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0044
dbscSNV1_RF	Benign	0.65
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: rs41263993; hg19: chr1-32669645; COSMIC: COSV52211938; COSMIC: COSV52211938;