Genetic Variant CCNH:c.760+132T>C (chr5-87401570-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_001239.4(CCNH):c.760+132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 636,916 control chromosomes in the GnomAD database, including 55,081 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 0.38 ( 11242 hom., cov: 32)

Exomes 𝑓: 0.42 ( 43839 hom. )

Consequence

CCNH
NM_001239.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.656

Publications

11 publications found

Variant links:

Genes affected

CCNH (HGNC:1594): (cyclin H) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. They participate in two different transcriptional regulation processes, suggesting an important link between basal transcription control and the cell cycle machinery. A pseudogene of this gene is found on chromosome 4. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Nov 2010]

CCNH 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=-0.68).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNH	NM_001239.4 link	c.760+132T>C		intron_variant	Intron 6 of 8	ENST00000256897.9	NP_001230.1	P51946

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNH	ENST00000256897.9 link	c.760+132T>C		intron_variant	Intron 6 of 8	1	NM_001239.4	ENSP00000256897.4		P51946

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57499

AN:

151880

Hom.:

11239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.473

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.420

GnomAD4 exome

AF:

0.420

AC:

203873

AN:

484918

Hom.:

43839

AF XY:

0.427

AC XY:

112252

AN XY:

263100

show subpopulations

African (AFR)

AF:

0.281

AC:

3399

AN:

12100

American (AMR)

AF:

0.379

AC:

6219

AN:

16426

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

7138

AN:

16308

East Asian (EAS)

AF:

0.416

AC:

12274

AN:

29512

South Asian (SAS)

AF:

0.491

AC:

23760

AN:

48348

European-Finnish (FIN)

AF:

0.396

AC:

12864

AN:

32462

Middle Eastern (MID)

AF:

0.540

AC:

1119

AN:

2074

European-Non Finnish (NFE)

AF:

0.418

AC:

125726

AN:

300666

Other (OTH)

AF:

0.421

AC:

11374

AN:

27022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5377

10754

16132

21509

26886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.378

AC:

57511

AN:

151998

Hom.:

11242

Cov.:

AF XY:

0.380

AC XY:

28237

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.278

AC:

11527

AN:

41490

American (AMR)

AF:

0.379

AC:

5791

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

1533

AN:

3466

East Asian (EAS)

AF:

0.499

AC:

2574

AN:

5158

South Asian (SAS)

AF:

0.475

AC:

2289

AN:

4820

European-Finnish (FIN)

AF:

0.385

AC:

4058

AN:

10540

Middle Eastern (MID)

AF:

0.476

AC:

138

AN:

290

European-Non Finnish (NFE)

AF:

0.417

AC:

28315

AN:

67926

Other (OTH)

AF:

0.421

AC:

889

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1816

3632

5448

7264

9080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.384

Hom.:

1853

Bravo

AF:

0.377

Asia WGS

AF:

0.437

AC:

1509

AN:

3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.66

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