5-87399457-A-G

Variant names:

Variant summary

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

The NM_001239.4(CCNH):c.809T>C(p.Val270Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,612,358 control chromosomes in the GnomAD database, including 32,656 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V270G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.17 ( 2605 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30051 hom. )

Consequence

CCNH
NM_001239.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.47

Publications

70 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0016247034).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNH	NM_001239.4	MANE Select	c.809T>C	p.Val270Ala	missense	Exon 7 of 9	NP_001230.1	P51946
CCNH	NM_001363539.2		c.809T>C	p.Val270Ala	missense	Exon 7 of 9	NP_001350468.1	A0A2R8YEM2
CCNH	NM_001364075.2		c.809T>C	p.Val270Ala	missense	Exon 7 of 9	NP_001351004.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNH	ENST00000256897.9	TSL:1 MANE Select	c.809T>C	p.Val270Ala	missense	Exon 7 of 9	ENSP00000256897.4	P51946
CCNH	ENST00000508855.5	TSL:1	c.587T>C	p.Val196Ala	missense	Exon 6 of 7	ENSP00000426454.1	D6RG18
CCNH	ENST00000504878.1	TSL:1	c.587T>C	p.Val196Ala	missense	Exon 7 of 9	ENSP00000426075.1	D6RHI7

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

26026

AN:

152020

Hom.:

2603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0790

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.0879

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.206

GnomAD2 exomes

AF:

0.180

AC:

45218

AN:

250990

AF XY:

0.184

show subpopulations

Gnomad AFR exome

AF:

0.0774

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.0883

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.212

GnomAD4 exome

AF:

0.197

AC:

287881

AN:

1460220

Hom.:

30051

Cov.:

AF XY:

0.197

AC XY:

143216

AN XY:

726502

show subpopulations

African (AFR)

AF:

0.0788

AC:

2635

AN:

33458

American (AMR)

AF:

0.111

AC:

4951

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

5857

AN:

26118

East Asian (EAS)

AF:

0.0862

AC:

3421

AN:

39684

South Asian (SAS)

AF:

0.142

AC:

12204

AN:

86220

European-Finnish (FIN)

AF:

0.259

AC:

13832

AN:

53308

Middle Eastern (MID)

AF:

0.215

AC:

1238

AN:

5768

European-Non Finnish (NFE)

AF:

0.209

AC:

232059

AN:

1110610

Other (OTH)

AF:

0.194

AC:

11684

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

11310

22620

33930

45240

56550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7704

15408

23112

30816

38520

<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:

0.171

AC:

26029

AN:

152138

Hom.:

2605

Cov.:

AF XY:

0.172

AC XY:

12795

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0787

AC:

3268

AN:

41518

American (AMR)

AF:

0.164

AC:

2511

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

762

AN:

3472

East Asian (EAS)

AF:

0.0875

AC:

454

AN:

5186

South Asian (SAS)

AF:

0.134

AC:

648

AN:

4822

European-Finnish (FIN)

AF:

0.261

AC:

2760

AN:

10566

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14939

AN:

67980

Other (OTH)

AF:

0.207

AC:

438

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1084

2167

3251

4334

5418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.204

Hom.:

10493

Bravo

AF:

0.159

TwinsUK

AF:

0.208

AC:

770

ALSPAC

AF:

0.213

AC:

821

ESP6500AA

AF:

0.0801

AC:

353

ESP6500EA

AF:

0.224

AC:

1925

ExAC

AF:

0.182

AC:

22049

Asia WGS

AF:

0.114

AC:

396

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

PhyloP100

8.5

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.24

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0030

Polyphen

0.96

Vest4

0.19

MPC

0.77

ClinPred

0.015

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

Mutation Taster

=97/3

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