15-74256432-G-A

Position:

• chr15-74256432-G-A

Variant summary

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

The NM_025055.5(CCDC33):​c.186-6008G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,836 control chromosomes in the GnomAD database, including 8,892 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 0.33 (8892 hom., cov: 33)
• Consequence: CCDC33 NM_025055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC33	NM_025055.5	c.186-6008G>A		intron_variant		ENST00000398814.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC33	ENST00000398814.8	c.186-6008G>A		intron_variant		2	NM_025055.5	P2
CCDC33	ENST00000635913.2	c.840-6008G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50287 AN: 151716 Hom.: 8880 Cov.: 33

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.331 AC: 50318 AN: 151836 Hom.: 8892 Cov.: 33 AF XY: 0.334 AC XY: 24801 AN XY: 74196

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.292

Alfa AF: 0.282 Hom.: 8605

Bravo AF: 0.324

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.61
DANN	Benign	0.70

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: rs9783698; hg19: chr15-74548773;