rs2289205

chr3-53844589-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938

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 (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHDH	NM_018397.5	c.-131+1494G>A		intron_variant		ENST00000315251.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHDH	ENST00000315251.11	c.-131+1494G>A		intron_variant		1	NM_018397.5	P1
CHDH	ENST00000481668.5	c.-138G>A		5_prime_UTR_variant	1/3	2
CHDH	ENST00000467802.1	c.-131+124G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40750 AN: 152106 Hom.: 5789 Cov.: 33

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.: 21 Cov.: 0 AF XY: 0.237 AC XY: 95 AN XY: 400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.0909

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.268 AC: 40772 AN: 152228 Hom.: 5795 Cov.: 33 AF XY: 0.266 AC XY: 19783 AN XY: 74420

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.0663

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.267

Alfa AF: 0.305 Hom.: 11948

Bravo AF: 0.262

Asia WGS AF: 0.146 AC: 510 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.2
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs2289205; hg19: chr3-53878616; COSMIC: COSV55473759; COSMIC: COSV55473759;