rs2317133

chr3-56614264-G-A

Variant summary

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

The NM_001141947.3(CCDC66):c.1566+514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,916 control chromosomes in the GnomAD database, including 8,409 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 0.32 (8409 hom., cov: 32)
• Consequence: CCDC66 NM_001141947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750

Genes affected

CCDC66 (HGNC:27709): (coiled-coil domain containing 66) Enables microtubule binding activity. Involved in cilium assembly; microtubule bundle formation; and regulation of protein localization to cilium. Located in several cellular components, including Flemming body; microtubule cytoskeleton; and photoreceptor inner segment. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC66	NM_001141947.3	c.1566+514G>A		intron_variant		ENST00000394672.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC66	ENST00000394672.8	c.1566+514G>A		intron_variant		1	NM_001141947.3	A2

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49062 AN: 151804 Hom.: 8402 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.323 AC: 49113 AN: 151916 Hom.: 8409 Cov.: 32 AF XY: 0.328 AC XY: 24321 AN XY: 74252

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.321

Alfa AF: 0.290 Hom.: 863

Bravo AF: 0.338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.48

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: rs2317133; hg19: chr3-56648292;