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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3 link	c.11+16_11+17insAGGGGTAAGCAGGGGTAAGC		intron_variant	Intron 1 of 17	ENST00000394672.8	NP_001135419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8 link	c.-20_-19insGTAAGCAGGGGTAAGCAGGG		5_prime_UTR_variant	Exon 1 of 18	1	NM_001141947.3	ENSP00000378167.3

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 v4.3

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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3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCAGGGGTAAGCA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over