Genetic Variant CCDC66:n.-20_-19insGTAAGCAGGGGTAAGCAGGG (chr3-56557250-T-TGGGGTAAGCAGGGGTAAGCA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000341455.10(CCDC66):n.-20_-19insGTAAGCAGGGGTAAGCAGGG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,547,076 control chromosomes in the GnomAD database, including 2 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

CCDC66
ENST00000341455.10 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

Publications

3 publications found

Variant links:

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]

CCDC66 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341455.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CCDC66	NM_001141947.3	MANE Select	c.11+16_11+17insAGGGGTAAGCAGGGGTAAGC	intron	N/A	NP_001135419.1
CCDC66	NM_001353147.1		c.11+16_11+17insAGGGGTAAGCAGGGGTAAGC	intron	N/A	NP_001340076.1
CCDC66	NM_001353148.1		c.11+16_11+17insAGGGGTAAGCAGGGGTAAGC	intron	N/A	NP_001340077.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CCDC66	ENST00000341455.10	TSL:1	n.-20_-19insGTAAGCAGGGGTAAGCAGGG	non_coding_transcript_exon	Exon 1 of 18	ENSP00000343840.6
CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.-20_-19insGTAAGCAGGGGTAAGCAGGG	5_prime_UTR	Exon 1 of 18	ENSP00000378167.3
CCDC66	ENST00000326595.11	TSL:1	c.-103_-102insGTAAGCAGGGGTAAGCAGGG	5_prime_UTR	Exon 1 of 18	ENSP00000326050.7

Frequencies

GnomAD3 genomes

AF:

0.000725

AC:

109

AN:

150444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00146

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00106

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000739

Gnomad OTH

AF:

0.00194

GnomAD4 exome

AF:

0.000198

AC:

276

AN:

1396514

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

127

AN XY:

688724

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

31554

American (AMR)

AF:

0.000196

AC:

AN:

35640

Ashkenazi Jewish (ASJ)

AF:

0.000994

AC:

AN:

25140

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35704

South Asian (SAS)

AF:

0.000379

AC:

AN:

79180

European-Finnish (FIN)

AF:

0.0000205

AC:

AN:

48776

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.000119

AC:

128

AN:

1076894

Other (OTH)

AF:

0.000397

AC:

AN:

57938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000724

AC:

109

AN:

150562

Hom.:

Cov.:

AF XY:

0.000763

AC XY:

AN XY:

73418

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

40982

American (AMR)

AF:

0.00145

AC:

AN:

15138

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3462

East Asian (EAS)

AF:

0.000200

AC:

AN:

4988

South Asian (SAS)

AF:

0.00106

AC:

AN:

4696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000739

AC:

AN:

67626

Other (OTH)

AF:

0.00192

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000604

Hom.:

4713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=52/148

disease causing (fs/PTC)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over