Genetic Variant CCDC66:c.-21_-20insGTAAGCAGGG (chr3-56557250-T-TGGGGTAAGCA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001353153.1(CCDC66):c.-95_-92+6dupAGGGGTAAGC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 1,546,866 control chromosomes in the GnomAD database, including 517,371 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 44725 hom., cov: 0)

Exomes 𝑓: 0.82 ( 472646 hom. )

Consequence

CCDC66
NM_001353153.1 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 3-56557250-T-TGGGGTAAGCA is Benign according to our data. Variant chr3-56557250-T-TGGGGTAAGCA is described in ClinVar as Benign. ClinVar VariationId is 402505.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353153.1. 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+7_11+16dupAGGGGTAAGC	intron	N/A	NP_001135419.1
CCDC66	NM_001353147.1		c.11+7_11+16dupAGGGGTAAGC	intron	N/A	NP_001340076.1
CCDC66	NM_001353148.1		c.11+7_11+16dupAGGGGTAAGC	intron	N/A	NP_001340077.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.-21_-20insGTAAGCAGGG	5_prime_UTR	Exon 1 of 18	ENSP00000378167.3
CCDC66	ENST00000326595.11	TSL:1	c.-104_-103insGTAAGCAGGG	5_prime_UTR	Exon 1 of 18	ENSP00000326050.7
CCDC66	ENST00000341455.10	TSL:1	n.-21_-20insGTAAGCAGGG	non_coding_transcript_exon	Exon 1 of 18	ENSP00000343840.6

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

114724

AN:

150364

Hom.:

44711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.630

Gnomad AMI

AF:

0.843

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.826

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.837

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.854

Gnomad OTH

AF:

0.755

GnomAD4 exome

AF:

0.818

AC:

1142155

AN:

1396384

Hom.:

472646

Cov.:

AF XY:

0.812

AC XY:

558958

AN XY:

688646

show subpopulations

African (AFR)

AF:

0.610

AC:

19254

AN:

31550

American (AMR)

AF:

0.760

AC:

27094

AN:

35636

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

20637

AN:

25138

East Asian (EAS)

AF:

0.572

AC:

20426

AN:

35704

South Asian (SAS)

AF:

0.566

AC:

44793

AN:

79164

European-Finnish (FIN)

AF:

0.838

AC:

40884

AN:

48762

Middle Eastern (MID)

AF:

0.736

AC:

4187

AN:

5688

European-Non Finnish (NFE)

AF:

0.854

AC:

919154

AN:

1076808

Other (OTH)

AF:

0.789

AC:

45726

AN:

57934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

11050

22099

33149

44198

55248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20646

41292

61938

82584

103230

<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:

0.763

AC:

114785

AN:

150482

Hom.:

44725

Cov.:

AF XY:

0.758

AC XY:

55644

AN XY:

73378

show subpopulations

African (AFR)

AF:

0.629

AC:

25758

AN:

40942

American (AMR)

AF:

0.783

AC:

11855

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.826

AC:

2861

AN:

3462

East Asian (EAS)

AF:

0.557

AC:

2775

AN:

4984

South Asian (SAS)

AF:

0.540

AC:

2537

AN:

4694

European-Finnish (FIN)

AF:

0.837

AC:

8694

AN:

10382

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.854

AC:

57746

AN:

67602

Other (OTH)

AF:

0.752

AC:

1568

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1199

2399

3598

4798

5997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.679

Hom.:

4713

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=131/69

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCA

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