rs9001

Variant names:

• chr3-53823890-T-G
• rs9001
• NM_018397.5:c.119A>C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E40G) has been classified as Uncertain significance.

• 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
• Publications: 52 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHDH	NM_018397.5	c.119A>C	p.Glu40Ala	missense_variant	Exon 3 of 9	ENST00000315251.11	NP_060867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHDH	ENST00000315251.11	c.119A>C	p.Glu40Ala	missense_variant	Exon 3 of 9	1	NM_018397.5	ENSP00000319851.5
CHDH	ENST00000481668.5	c.119A>C	p.Glu40Ala	missense_variant	Exon 3 of 3	2		ENSP00000418273.1
CHDH	ENST00000467802.1	c.119A>C	p.Glu40Ala	missense_variant	Exon 3 of 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

GnomAD2 exomes AF: 0.153 AC: 29276 AN: 191492 AF XY: 0.142

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 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

African (AFR) AF: 0.304 AC: 9958 AN: 32752

American (AMR) AF: 0.279 AC: 11558 AN: 41430

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3393 AN: 25546

East Asian (EAS) AF: 0.397 AC: 15108 AN: 38022

South Asian (SAS) AF: 0.144 AC: 11990 AN: 83486

European-Finnish (FIN) AF: 0.134 AC: 5083 AN: 37806

Middle Eastern (MID) AF: 0.139 AC: 793 AN: 5722

European-Non Finnish (NFE) AF: 0.0806 AC: 89008 AN: 1104344

Other (OTH) AF: 0.127 AC: 7558 AN: 59410

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

African (AFR) AF: 0.303 AC: 12567 AN: 41524

American (AMR) AF: 0.233 AC: 3561 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1842 AN: 5142

South Asian (SAS) AF: 0.148 AC: 714 AN: 4828

European-Finnish (FIN) AF: 0.131 AC: 1387 AN: 10600

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0832 AC: 5658 AN: 67984

Other (OTH) AF: 0.169 AC: 356 AN: 2112

Alfa AF: 0.143 Hom.: 774

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;.;.
PhyloP100		1.5
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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