rs9001

Positions:

• chr3-53823890-T-G

Variant summary

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

The NM_018397.5(CHDH):​c.119A>C​(p.Glu40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,580,680 control chromosomes in the GnomAD database, including 15,388 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.17 (3214 hom., cov: 35)
  • Exomes 𝑓: 0.11 (12174 hom.)
• Consequence: CHDH NM_018397.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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=0.0044822097).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHDH	NM_018397.5	c.119A>C	p.Glu40Ala	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.119A>C	p.Glu40Ala	missense_variant	3/9	1	NM_018397.5	ENSP00000319851.5
CHDH	ENST00000481668.5	c.119A>C	p.Glu40Ala	missense_variant	3/3	2		ENSP00000418273.1
CHDH	ENST00000467802.1	c.119A>C	p.Glu40Ala	missense_variant	3/3	2		ENSP00000419863.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26559 AN: 152040 Hom.: 3204 Cov.: 35

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0832

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.153 AC: 29276 AN: 191492 Hom.: 3089 AF XY: 0.142 AC XY: 15128 AN XY: 106746

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.330

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.0756

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.108 AC: 154449 AN: 1428518 Hom.: 12174 Cov.: 36 AF XY: 0.108 AC XY: 76651 AN XY: 709976

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.175 AC: 26600 AN: 152162 Hom.: 3214 Cov.: 35 AF XY: 0.179 AC XY: 13299 AN XY: 74380

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0832

Gnomad4 OTH AF: 0.169

Alfa AF: 0.138 Hom.: 678

Bravo AF: 0.190

TwinsUK AF: 0.0806 AC: 299

ALSPAC AF: 0.0765 AC: 295

ESP6500AA AF: 0.228 AC: 816

ESP6500EA AF: 0.0639 AC: 469

ExAC AF: 0.123 AC: 13959

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.61	T;T;T
MetaRNN	Benign	0.0045	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.095
Sift	Benign	0.033	D;T;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.022	B;.;.
Vest4		0.12
MPC		0.31
ClinPred		0.011	T
GERP RS		3.8
Varity_R		0.12
gMVP		0.58

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: rs9001; hg19: chr3-53857917; COSMIC: COSV59456271;