chr3-53823776-A-C

Position:

• chr3-53823776-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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]

ACMG classification

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	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	UniProt
CHDH	ENST00000315251.11	c.233T>G	p.Leu78Arg	missense_variant	3/9	1	NM_018397.5	ENSP00000319851	P1
CHDH	ENST00000481668.5	c.233T>G	p.Leu78Arg	missense_variant	3/3	2		ENSP00000418273
CHDH	ENST00000467802.1	c.233T>G	p.Leu78Arg	missense_variant	3/3	2		ENSP00000419863

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117797 AN: 152062 Hom.: 46243 Cov.: 36

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

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.: 90 AF XY: 0.726 AC XY: 508713 AN XY: 700886

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.: 36 AF XY: 0.778 AC XY: 57861 AN XY: 74402

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	T
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	N
LIST_S2	Benign	0.0074	T;T;T
MetaRNN	Benign	0.0000012	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.26	T
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	T
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

Other links and lift over

dbSNP: rs12676; hg19: chr3-53857803; COSMIC: COSV59456558;