1-32204190-G-A

Position:

• chr1-32204190-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_024296.5(CCDC28B):​c.336G>A​(p.Lys112=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,614,074 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (3 hom.)
• Consequence: CCDC28B NM_024296.5 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC28B	NM_024296.5	c.336G>A	p.Lys112=	synonymous_variant	4/6	ENST00000373602.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC28B	ENST00000373602.10	c.336G>A	p.Lys112=	synonymous_variant	4/6	1	NM_024296.5	P1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000442 AC: 111 AN: 251300 Hom.: 2 AF XY: 0.000449 AC XY: 61 AN XY: 135832

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000686

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.000410 AC: 599 AN: 1461800 Hom.: 3 Cov.: 32 AF XY: 0.000419 AC XY: 305 AN XY: 727216

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000424

Gnomad4 OTH exome AF: 0.000613

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74452

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000457 Hom.: 0

Bravo AF: 0.000329

EpiCase AF: 0.00120

EpiControl AF: 0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 06, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199647520; hg19: chr1-32669791;