3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCA

Variant names:

• chr3-56557250-T-TGGGGTAAGCA
• rs60235683
• ENST00000341455.10:n.-21_-20insGTAAGCAGGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000341455.10(CCDC66):​n.-21_-20insGTAAGCAGGG 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 0.813 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 ENST00000341455.10 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.359
• 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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3	c.11+7_11+16dupAGGGGTAAGC		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	c.-21_-20insGTAAGCAGGG		5_prime_UTR_variant	Exon 1 of 18	1	NM_001141947.3	ENSP00000378167.3

Frequencies

GnomAD3 genomes AF: 0.763 AC: 114724 AN: 150364 Hom.: 44711 Cov.: 0

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.: 66 AF XY: 0.812 AC XY: 558958 AN XY: 688646

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

GnomAD4 genome AF: 0.763 AC: 114785 AN: 150482 Hom.: 44725 Cov.: 0 AF XY: 0.758 AC XY: 55644 AN XY: 73378

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

Alfa AF: 0.679 Hom.: 4713

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 1498/2178=68.77% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=131/69	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs60235683; hg19: chr3-56591278; COSMIC: COSV58301087; COSMIC: COSV58301087;