Genetic Variant CHDH:p.Ala240Ala (chr3-53822626-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_018397.5(CHDH):c.720G>A(p.Ala240Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,608,824 control chromosomes in the GnomAD database, including 222,062 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 ( 16531 hom., cov: 33)

Exomes 𝑓: 0.53 ( 205531 hom. )

Consequence

CHDH
NM_018397.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.23

Publications

23 publications found

Variant links:

Genes affected

CHDH (HGNC:24288): (choline dehydrogenase) The protein encoded by this gene is a choline dehydrogenase that localizes to the mitochondrion. Variations in this gene can affect susceptibility to choline deficiency. A few transcript variants have been found for this gene, but the full-length nature of only one has been characterized to date. [provided by RefSeq, Dec 2010]

CHDH 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=-0.87).

BP7

Synonymous conserved (PhyloP=-3.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHDH	NM_018397.5 link	c.720G>A	p.Ala240Ala	synonymous_variant	Exon 4 of 9	ENST00000315251.11	NP_060867.2	Q8NE62

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHDH	ENST00000315251.11 link	c.720G>A	p.Ala240Ala	synonymous_variant	Exon 4 of 9	1	NM_018397.5	ENSP00000319851.5		Q8NE62

Frequencies

GnomAD3 genomes

AF:

0.444

AC:

67481

AN:

152002

Hom.:

16521

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.475

Gnomad EAS

AF:

0.575

Gnomad SAS

AF:

0.576

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.472

GnomAD2 exomes

AF:

0.508

AC:

125750

AN:

247416

AF XY:

0.517

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.477

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.537

Gnomad OTH exome

AF:

0.514

GnomAD4 exome

AF:

0.528

AC:

769107

AN:

1456704

Hom.:

205531

Cov.:

AF XY:

0.531

AC XY:

384676

AN XY:

724710

show subpopulations

African (AFR)

AF:

0.210

AC:

7020

AN:

33444

American (AMR)

AF:

0.467

AC:

20857

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12441

AN:

26114

East Asian (EAS)

AF:

0.543

AC:

21551

AN:

39668

South Asian (SAS)

AF:

0.583

AC:

50229

AN:

86216

European-Finnish (FIN)

AF:

0.477

AC:

23581

AN:

49424

Middle Eastern (MID)

AF:

0.459

AC:

2643

AN:

5762

European-Non Finnish (NFE)

AF:

0.540

AC:

599631

AN:

1111116

Other (OTH)

AF:

0.517

AC:

31154

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

18712

37424

56137

74849

93561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16912

33824

50736

67648

84560

<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:

0.444

AC:

67507

AN:

152120

Hom.:

16531

Cov.:

AF XY:

0.443

AC XY:

32971

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.221

AC:

9173

AN:

41522

American (AMR)

AF:

0.468

AC:

7151

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

1649

AN:

3470

East Asian (EAS)

AF:

0.575

AC:

2969

AN:

5162

South Asian (SAS)

AF:

0.578

AC:

2787

AN:

4824

European-Finnish (FIN)

AF:

0.480

AC:

5080

AN:

10576

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.544

AC:

37010

AN:

67974

Other (OTH)

AF:

0.474

AC:

1000

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1781

3562

5343

7124

8905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.479

Hom.:

11852

Bravo

AF:

0.431

Asia WGS

AF:

0.553

AC:

1924

AN:

3478

EpiCase

AF:

0.527

EpiControl

AF:

0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.22

(source)

DANN

Benign

0.52

PhyloP100

-3.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=98/2

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