rs2317133

Variant names:

• chr3-56614264-G-A
• rs2317133
• NM_001141947.3:c.1566+514G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141947.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC66	NM_001141947.3	MANE Select	c.1566+514G>A		intron	N/A	NP_001135419.1	A2RUB6-1
	CCDC66	NM_001353147.1		c.1566+514G>A		intron	N/A	NP_001340076.1
	CCDC66	NM_001353148.1		c.1548+514G>A		intron	N/A	NP_001340077.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.1566+514G>A		intron	N/A	ENSP00000378167.3	A2RUB6-1
	CCDC66	ENST00000326595.11	TSL:1	c.1464+514G>A		intron	N/A	ENSP00000326050.7	A2RUB6-3
	CCDC66	ENST00000341455.10	TSL:1	n.*854+514G>A		intron	N/A	ENSP00000343840.6	F8WCY0

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

African (AFR) AF: 0.393 AC: 16276 AN: 41434

American (AMR) AF: 0.438 AC: 6684 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2503 AN: 5168

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4820

European-Finnish (FIN) AF: 0.312 AC: 3287 AN: 10530

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17438 AN: 67938

Other (OTH) AF: 0.321 AC: 674 AN: 2102

Alfa AF: 0.294 Hom.: 917

Bravo AF: 0.338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2317133; hg19: chr3-56648292;