Genetic Variant CHDH:c.-131+1494G>A (chr3-53844589-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018397.5(CHDH):c.-131+1494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,760 control chromosomes in the GnomAD database, including 5,816 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 0.27 ( 5795 hom., cov: 33)

Exomes 𝑓: 0.26 ( 21 hom. )

Consequence

CHDH
NM_018397.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.938

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018397.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHDH	NM_018397.5	MANE Select	c.-131+1494G>A		intron	N/A	NP_060867.2	Q8NE62

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHDH	ENST00000315251.11	TSL:1 MANE Select	c.-131+1494G>A	intron	N/A	ENSP00000319851.5	Q8NE62
CHDH	ENST00000481668.5	TSL:2	c.-138G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000418273.1	C9J7D8
CHDH	ENST00000481668.5	TSL:2	c.-138G>A	5_prime_UTR	Exon 1 of 3	ENSP00000418273.1	C9J7D8

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40750

AN:

152106

Hom.:

5789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.0662

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.256

AC:

136

AN:

532

Hom.:

Cov.:

AF XY:

0.237

AC XY:

AN XY:

400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0909

AC:

AN:

South Asian (SAS)

AF:

0.200

AC:

AN:

European-Finnish (FIN)

AF:

0.281

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.267

AC:

111

AN:

416

Other (OTH)

AF:

0.367

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.268

AC:

40772

AN:

152228

Hom.:

5795

Cov.:

AF XY:

0.266

AC XY:

19783

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.208

AC:

8637

AN:

41526

American (AMR)

AF:

0.245

AC:

3749

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1274

AN:

3470

East Asian (EAS)

AF:

0.0663

AC:

344

AN:

5188

South Asian (SAS)

AF:

0.212

AC:

1024

AN:

4824

European-Finnish (FIN)

AF:

0.319

AC:

3384

AN:

10598

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21413

AN:

68004

Other (OTH)

AF:

0.267

AC:

564

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1546

3092

4638

6184

7730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.296

Hom.:

26731

Bravo

AF:

0.262

Asia WGS

AF:

0.146

AC:

510

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.2

(source)

DANN

Benign

0.73

PhyloP100

-0.94

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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