rs6425793

Positions:

• chr1-32202827-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024296.5(CCDC28B):​c.164+728A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 155,446 control chromosomes in the GnomAD database, including 4,410 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4286 hom., cov: 32)
  • Exomes 𝑓: 0.27 (124 hom.)
• Consequence: CCDC28B NM_024296.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC28B	NM_024296.5	c.164+728A>G		intron_variant		ENST00000373602.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC28B	ENST00000373602.10	c.164+728A>G		intron_variant		1	NM_024296.5	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32529 AN: 152086 Hom.: 4285 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.273 AC: 886 AN: 3242 Hom.: 124 Cov.: 0 AF XY: 0.268 AC XY: 470 AN XY: 1752

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.214 AC: 32536 AN: 152204 Hom.: 4286 Cov.: 32 AF XY: 0.211 AC XY: 15737 AN XY: 74410

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.228

Alfa AF: 0.253 Hom.: 777

Bravo AF: 0.209

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs6425793; hg19: chr1-32668428;