Variant rs12676 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018397.5(CHDH):c.233T>G(p.Leu78Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,568,132 control chromosomes in the GnomAD database, including 420,266 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.77 ( 46306 hom., cov: 36)

Exomes 𝑓: 0.72 ( 373960 hom. )

Consequence

CHDH
NM_018397.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1755087E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHDH	NM_018397.5 linkuse as main transcript	c.233T>G	p.Leu78Arg	missense_variant	3/9	ENST00000315251.11	NP_060867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CHDH	ENST00000315251.11 linkuse as main transcript	c.233T>G	p.Leu78Arg	missense_variant	3/9	1	NM_018397.5	ENSP00000319851	P1
CHDH	ENST00000481668.5 linkuse as main transcript	c.233T>G	p.Leu78Arg	missense_variant	3/3	2		ENSP00000418273
CHDH	ENST00000467802.1 linkuse as main transcript	c.233T>G	p.Leu78Arg	missense_variant	3/3	2		ENSP00000419863

Frequencies

GnomAD3 genomes

AF:

0.775

AC:

117797

AN:

152062

Hom.:

46243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.803

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.713

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.775

GnomAD3 exomes

AF:

0.773

AC:

136270

AN:

176366

Hom.:

53401

AF XY:

0.768

AC XY:

73708

AN XY:

96036

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.852

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.820

Gnomad FIN exome

AF:

0.688

Gnomad NFE exome

AF:

0.702

Gnomad OTH exome

AF:

0.745

GnomAD4 exome

AF:

0.724

AC:

1024843

AN:

1415952

Hom.:

373960

Cov.:

AF XY:

0.726

AC XY:

508713

AN XY:

700886

show subpopulations

Gnomad4 AFR exome

AF:

0.880

Gnomad4 AMR exome

AF:

0.846

Gnomad4 ASJ exome

AF:

0.685

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.815

Gnomad4 FIN exome

AF:

0.692

Gnomad4 NFE exome

AF:

0.700

Gnomad4 OTH exome

AF:

0.742

GnomAD4 genome

AF:

0.775

AC:

117920

AN:

152180

Hom.:

46306

Cov.:

AF XY:

0.778

AC XY:

57861

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.875

Gnomad4 AMR

AF:

0.804

Gnomad4 ASJ

AF:

0.690

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.829

Gnomad4 FIN

AF:

0.692

Gnomad4 NFE

AF:

0.705

Gnomad4 OTH

AF:

0.777

Alfa

AF:

0.697

Hom.:

9927

Bravo

AF:

0.786

TwinsUK

AF:

0.704

AC:

2611

ALSPAC

AF:

0.714

AC:

2751

ESP6500AA

AF:

0.879

AC:

3654

ESP6500EA

AF:

0.718

AC:

5839

ExAC

AF:

0.728

AC:

80241

Asia WGS

AF:

0.919

AC:

3196

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.15

DANN

Benign

0.48

DEOGEN2

Benign

0.16

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.0074

T;T;T

MetaRNN

Benign

0.0000012

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.084

Sift

Benign

0.39

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.13

MPC

0.39

ClinPred

0.020

GERP RS

-12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over