rs2959008

Positions:

• chr15-74324236-A-G

Variant summary

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

The NM_025055.5(CCDC33):​c.1291-5953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,722 control chromosomes in the GnomAD database, including 25,040 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 0.56 (25040 hom., cov: 29)
• Consequence: CCDC33 NM_025055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913

Genes affected

CCDC33 (HGNC:26552): (coiled-coil domain containing 33) Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC33	NM_025055.5	c.1291-5953A>G		intron_variant		ENST00000398814.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC33	ENST00000398814.8	c.1291-5953A>G		intron_variant		2	NM_025055.5	P2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84888 AN: 151604 Hom.: 25038 Cov.: 29

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.552

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.560 AC: 84924 AN: 151722 Hom.: 25040 Cov.: 29 AF XY: 0.554 AC XY: 41101 AN XY: 74130

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.547

Alfa AF: 0.611 Hom.: 4933

Bravo AF: 0.550

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.33

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: rs2959008; hg19: chr15-74616577;