Genetic Variant NM_018246.3:c.168+98T>C (chr8-27756621-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018246.3(CCDC25):c.168+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 815,666 control chromosomes in the GnomAD database, including 79,847 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 0.44 ( 14691 hom., cov: 32)

Exomes 𝑓: 0.44 ( 65156 hom. )

Consequence

CCDC25
NM_018246.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.894

Publications

7 publications found

Variant links:

Genes affected

CCDC25 (HGNC:25591): (coiled-coil domain containing 25) Enables DNA binding activity. Involved in positive regulation of cell motility. Located in endomembrane system. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC25 links:

ENSG00000253875 (HGNC:):

ENSG00000253875 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018246.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC25	NM_018246.3	MANE Select	c.168+98T>C	intron	N/A	NP_060716.2	Q86WR0-1
CCDC25	NM_001304532.2		c.-36-4034T>C	intron	N/A	NP_001291461.1	Q86WR0-2
CCDC25	NM_001304530.2		c.-36-4034T>C	intron	N/A	NP_001291459.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC25	ENST00000356537.9	TSL:1 MANE Select	c.168+98T>C	intron	N/A	ENSP00000348933.4	Q86WR0-1
CCDC25	ENST00000517979.1	TSL:1	n.*335+98T>C	intron	N/A	ENSP00000428499.1	E5RI21
CCDC25	ENST00000520202.5	TSL:1	n.117-4034T>C	intron	N/A	ENSP00000428587.1	Q0VGD4

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

66184

AN:

151900

Hom.:

14661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.422

GnomAD4 exome

AF:

0.437

AC:

290264

AN:

663646

Hom.:

65156

Cov.:

AF XY:

0.433

AC XY:

152557

AN XY:

352038

show subpopulations

African (AFR)

AF:

0.448

AC:

7558

AN:

16878

American (AMR)

AF:

0.593

AC:

19610

AN:

33062

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

5299

AN:

18980

East Asian (EAS)

AF:

0.627

AC:

21543

AN:

34334

South Asian (SAS)

AF:

0.414

AC:

25464

AN:

61564

European-Finnish (FIN)

AF:

0.383

AC:

18902

AN:

49330

Middle Eastern (MID)

AF:

0.299

AC:

898

AN:

3004

European-Non Finnish (NFE)

AF:

0.428

AC:

176745

AN:

413178

Other (OTH)

AF:

0.428

AC:

14245

AN:

33316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

7595

15190

22786

30381

37976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2644

5288

7932

10576

13220

<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:

0.436

AC:

66275

AN:

152020

Hom.:

14691

Cov.:

AF XY:

0.435

AC XY:

32314

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.437

AC:

18126

AN:

41476

American (AMR)

AF:

0.500

AC:

7638

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

935

AN:

3472

East Asian (EAS)

AF:

0.630

AC:

3253

AN:

5166

South Asian (SAS)

AF:

0.428

AC:

2059

AN:

4814

European-Finnish (FIN)

AF:

0.370

AC:

3908

AN:

10550

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.425

AC:

28884

AN:

67948

Other (OTH)

AF:

0.426

AC:

899

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1911

3822

5734

7645

9556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.430

Hom.:

52012

Bravo

AF:

0.449

Asia WGS

AF:

0.554

AC:

1924

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.42

(source)

DANN

Benign

0.23

PhyloP100

-0.89

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over