Genetic Variant CCDC57:c.*226T>G (chr17-82101456-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394669.1(CCDC57):c.*226T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 497,564 control chromosomes in the GnomAD database, including 70,177 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 0.55 ( 23679 hom., cov: 33)

Exomes 𝑓: 0.50 ( 46498 hom. )

Consequence

CCDC57
NM_001394669.1 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Publications

21 publications found

Variant links:

Genes affected

CCDC57 (HGNC:27564): (coiled-coil domain containing 57) Involved in several processes, including G2/M transition of mitotic cell cycle; cilium assembly; and microtubule cytoskeleton organization. Located in centriolar satellite; centriole; and spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CCDC57 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394669.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC57	NM_001394669.1	MANE Select	c.*226T>G	downstream_gene	N/A	NP_001381598.1	A0A590UJT6
CCDC57	NM_001394670.1		c.*226T>G	downstream_gene	N/A	NP_001381599.1	A0A590UJT6
CCDC57	NM_198082.4		c.*226T>G	downstream_gene	N/A	NP_932348.2	Q2TAC2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC57	ENST00000694881.1	MANE Select	c.*226T>G	downstream_gene	N/A	ENSP00000511565.1	A0A590UJT6
CCDC57	ENST00000665763.1		c.*226T>G	downstream_gene	N/A	ENSP00000499556.1	A0A590UJT6
CCDC57	ENST00000875325.1		c.*226T>G	downstream_gene	N/A	ENSP00000545384.1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83163

AN:

152012

Hom.:

23677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.635

Gnomad AMI

AF:

0.606

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.530

GnomAD4 exome

AF:

0.502

AC:

173478

AN:

345434

Hom.:

46498

Cov.:

AF XY:

0.498

AC XY:

89340

AN XY:

179404

show subpopulations

African (AFR)

AF:

0.618

AC:

5135

AN:

8306

American (AMR)

AF:

0.353

AC:

3236

AN:

9160

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

4423

AN:

11586

East Asian (EAS)

AF:

0.110

AC:

2601

AN:

23578

South Asian (SAS)

AF:

0.430

AC:

11803

AN:

27454

European-Finnish (FIN)

AF:

0.535

AC:

13930

AN:

26054

Middle Eastern (MID)

AF:

0.415

AC:

706

AN:

1700

European-Non Finnish (NFE)

AF:

0.560

AC:

121045

AN:

216194

Other (OTH)

AF:

0.495

AC:

10599

AN:

21402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

3635

7270

10906

14541

18176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.547

AC:

83194

AN:

152130

Hom.:

23679

Cov.:

AF XY:

0.539

AC XY:

40126

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.634

AC:

26294

AN:

41480

American (AMR)

AF:

0.420

AC:

6433

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1375

AN:

3470

East Asian (EAS)

AF:

0.119

AC:

616

AN:

5182

South Asian (SAS)

AF:

0.431

AC:

2077

AN:

4824

European-Finnish (FIN)

AF:

0.535

AC:

5664

AN:

10584

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.573

AC:

38947

AN:

67972

Other (OTH)

AF:

0.525

AC:

1110

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1895

3790

5684

7579

9474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.536

Hom.:

14108

Bravo

AF:

0.537

Asia WGS

AF:

0.287

AC:

1000

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.12

(source)

DANN

Benign

0.23

PhyloP100

-1.9

PromoterAI

-0.034

Neutral

(source)

Mutation Taster

=98/2

polymorphism

(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