Genetic Variant CCDC86:p.Pro125Pro (chr11-60842499-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_024098.4(CCDC86):c.375A>G(p.Pro125Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,613,780 control chromosomes in the GnomAD database, including 35,700 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 0.19 ( 2845 hom., cov: 33)

Exomes 𝑓: 0.21 ( 32855 hom. )

Consequence

CCDC86
NM_024098.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.56

Publications

17 publications found

Variant links:

Genes affected

CCDC86 (HGNC:28359): (coiled-coil domain containing 86) Enables RNA binding activity. Located in chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC86 links:

ENSG00000255959 (HGNC:):

ENSG00000255959 links:

CCDC86-AS1 (HGNC:56314): (CCDC86 antisense RNA 1)

CCDC86-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP7

Synonymous conserved (PhyloP=-1.56 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC86	NM_024098.4 link	c.375A>G	p.Pro125Pro	synonymous_variant	Exon 1 of 4	ENST00000227520.10	NP_077003.1	Q9H6F5-1
CCDC86-AS1	NR_182293.1 link	n.317-519T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC86	ENST00000227520.10 link	c.375A>G	p.Pro125Pro	synonymous_variant	Exon 1 of 4	1	NM_024098.4	ENSP00000227520.5		Q9H6F5-1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29261

AN:

152022

Hom.:

2843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.198

GnomAD2 exomes

AF:

0.185

AC:

46378

AN:

250336

AF XY:

0.190

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.208

AC:

304726

AN:

1461640

Hom.:

32855

Cov.:

AF XY:

0.209

AC XY:

151954

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.180

AC:

6019

AN:

33476

American (AMR)

AF:

0.123

AC:

5496

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

7782

AN:

26134

East Asian (EAS)

AF:

0.127

AC:

5035

AN:

39700

South Asian (SAS)

AF:

0.219

AC:

18872

AN:

86258

European-Finnish (FIN)

AF:

0.124

AC:

6595

AN:

53182

Middle Eastern (MID)

AF:

0.258

AC:

1490

AN:

5768

European-Non Finnish (NFE)

AF:

0.216

AC:

240528

AN:

1112008

Other (OTH)

AF:

0.214

AC:

12909

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

15914

31828

47743

63657

79571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8240

16480

24720

32960

41200

<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:

0.192

AC:

29272

AN:

152140

Hom.:

2845

Cov.:

AF XY:

0.188

AC XY:

13979

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.180

AC:

7480

AN:

41508

American (AMR)

AF:

0.159

AC:

2437

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1011

AN:

3466

East Asian (EAS)

AF:

0.117

AC:

602

AN:

5166

South Asian (SAS)

AF:

0.208

AC:

1002

AN:

4822

European-Finnish (FIN)

AF:

0.115

AC:

1220

AN:

10606

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14786

AN:

67966

Other (OTH)

AF:

0.197

AC:

416

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1252

2505

3757

5010

6262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.208

Hom.:

2636

Bravo

AF:

0.194

Asia WGS

AF:

0.173

AC:

603

AN:

3478

EpiCase

AF:

0.229

EpiControl

AF:

0.229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.69

(source)

DANN

Benign

0.53

PhyloP100

-1.6

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over